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IL-6 Production (il-6 + production)
Selected AbstractsORIGINAL ARTICLE: Antiphospholipid Antibodies Limit Trophoblast Migration by Reducing IL-6 Production and STAT3 ActivityAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 5 2010Melissa J. Mulla Citation Mulla MJ, Myrtolli K, Brosens JJ, Chamley LW, Kwak-Kim JY, Paidas MJ, Abrahams VM. Antiphospholipid antibodies limit trophoblast migration by reducing IL-6 production and STAT3 activity. Am J Reprod Immunol 2010 Problem Women with antiphospholipid antibodies (aPL) are at risk of recurrent miscarriage and pre-eclampsia. aPL target the placenta by binding to ,2 -glycoprotein I (,2 GPI) expressed by the trophoblast. The objective of this study was to evaluate if and how aPL affect first trimester trophoblast migration. Method of study First trimester trophoblast cells were treated with anti-,2 GPI monoclonal antibodies. Migration was determined using a two-chamber assay. Interleukin (IL)-6 production was evaluated by RT-PCR and enzyme-linked immunosorbent assay, and signal transducer and activator of transcription 3 (STAT3) activation was assessed by western blot. Results Trophoblast cells constitutively secreted IL-6 in a time-dependent manner and this directly correlated with STAT3 phosphorylation. In the presence of anti-,2 GPI Abs, trophoblast IL-6 mRNA levels and secretion was downregulated in a Toll-like receptor 4/MyD88-independent manner and this correlated with a reduction in phosphorylated STAT3 levels. In addition, the anti-,2 GPI Abs reduced the migratory potential of trophoblast. Heparin was able to reverse aPL-dependent inhibition of trophoblast IL-6 secretion and migration. Conclusion This study demonstrates that aPL limit trophoblast cell migration by downregulating trophoblast IL-6 secretion and STAT3 activity. As heparin was unable to prevent these effects, our findings may explain why women with antiphospholipid syndrome, treated with heparin, remain at risk of developing obstetrical syndromes, associated with impaired deep placentation, such as pre-eclampsia. [source] TLR7 and CD40 cooperate in IL-6 production via enhanced JNK and AP-1 activationEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 2 2008Vanden Bush Abstract During vaccination or infection, adaptive and innate immune receptors of B cells are engaged by microbial antigens/ligands. A better understanding of how innate and adaptive signaling pathways interact could enlighten B lymphocyte biology as well as aid immunotherapy strategies and vaccine design. To address this goal, we examined the effects of TLR stimulation on BCR and CD40-induced B cell activation. Synergistic production of IL-6 was observed in both human and mouse primary B cells stimulated through B cell antigen receptors, CD40 and TLR7, and these two receptors also cooperated independently of BCR signals. The enhanced IL-6 production was dependent upon the activity of c-Jun kinase (JNK) and cFos. Dual stimulation through CD40 and TLR7 markedly enhanced JNK activity. The increased level of active JNK in dual-stimulated cells was accompanied by an increase in the level of active AP-1 monomers cJun and cFos. The stimulation of B cells through both CD40 and TLR7 therefore enhanced the production of cytokines through increased JNK signaling and AP-1 activity. In addition, the dual stimulation increased cFos/AP-1 species in stimulated cells, effectively expanding the repertoire of AP-1 dimers as compared to singly stimulated B cells. [source] p38 MAPK is a critical regulator of the constitutive and the ,4,integrin-regulated expression of IL-6 in human normal thymic epithelial cellsEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 11 2003Fabrizio Mainiero Abstract Cytokines and adhesion receptors are key mediators in the dialog occurring between thymic epithelial cells (TEC) and thymocytes and regulating T,cell maturation and epithelial embryonic differentiation. Among cytokines, IL-6 can be critical in the thymus, fostering proliferation, differentiation and/or survival of both TEC and thymocytes. We have previously reported in human normal TEC that clustering of the laminin receptor ,6,4 integrin induced by thymocyte contact or monoclonal antibody-mediated cross-linking regulates IL-6 gene expression via activation of NF-,B and NF-IL6 transactivators. Here we show that ,6,4 integrin activates p38 mitogen-activated protein kinase (MAPK) and that p38 is essential for IL-6 gene expression. In fact, ,4 cross-linking activated p38 and extracellular signal-regulated kinase (ERK) MAPK, Rac1, p21-activated protein kinase,1 (PAK1) and MAPK kinases (MKK),3/MKK6. However, pharmacological blockade of p38 or ERK demonstrated that p38 inhibition abrogated both basal and ,4,integrin-induced production of IL-6 preventing NF-,B and NF-IL6 activation, whereas ERK inhibition reduced IL-6 production, hampering only NF-,B activation. Overall, our results indicate that p38 MAPK and ,6,4,integrin, expressed by TEC throughout their life, are critical regulators of the intrathymic availability of a cytokine controlling fate and functions of cells governing development and maintenance of thymic architecture and immune responses. [source] Acylation of lysophosphatidylcholine plays a key role in the response of monocytes to lipopolysaccharideFEBS JOURNAL, Issue 13 2003Bernhard Schmid Mononuclear phagocytes play a pivotal role in the progression of septic shock by producing tumor necrosis factor-, (TNF-,) and other inflammatory mediators in response to lipopolysaccharide (LPS) from Gram-negative bacteria. Our previous studies have shown monocyte and macrophage activation correlate with changes in membrane phospholipid composition, mediated by acyltransferases. Interferon-, (IFN-,), which activates and primes these cells for enhanced inflammatory responses to LPS, was found to selectively activate lysophosphatidylcholine acyltransferase (LPCAT) (P < 0.05) but not lysophosphatidic acid acyltransferase (LPAAT) activity. When used to prime the human monocytic cell line MonoMac 6, the production of TNF-, and interleukin-6 (IL-6) was approximately five times greater in cells primed with IFN-, than unprimed cells. Two LPCAT inhibitors SK&F 98625 (diethyl 7-(3,4,5-triphenyl-2-oxo2,3-dihydro-imidazole-1-yl)heptane phosphonate) and YM 50201 (3-hydroxyethyl 5,3,-thiophenyl pyridine) strongly inhibited (up to 90%) TNF-, and IL-6 production in response to LPS in both unprimed MonoMac-6 cells and in cells primed with IFN-,. In similar experiments, these inhibitors also substantially decreased the response of both primed and unprimed peripheral blood mononuclear cells to LPS. Sequence-based amplification methods showed that SK&F 98625 inhibited TNF-, production by decreasing TNF-, mRNA levels in MonoMac-6 cells. Taken together, the data from these studies suggest that LPCAT is a key enzyme in both the pathways of activation (priming) and the inflammatory response to LPS in monocytes. [source] Effects of serotonin and catecholamine depletion on interleukin-6 activation and mood in human volunteersHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 6 2002Ben J. Harrison Abstract There is increasing evidence that depression and related neurotic illnesses are associated with alterations in immune function that may contribute to their pathogenesis. For example, clinical and experimental studies have shown that abnormal HPA-axis activation and monoamine neurotransmission may be related to an increased release of proinflammatory cytokines from stimulated lymphocytes in the periphery and brain. In the present investigation, the effects of tryptophan depletion (TD) on unstimulated plasma interleukin-6 (IL-6) concentrations were investigated in order to determine whether acute changes in serotonin (5-HT) neurotransmission would induce a proinflammatory response in healthy individuals. The effects of TD were compared with the analogous procedure of tyrosine depletion (TPD), which reduces catecholamine metabolism in humans. Thirteen female participants completed three experimental sessions: TD, TPD and a balanced-control condition (B). Mood-ratings and blood sampling were performed at baseline and 5,h after the administration of the mixtures. Analyses revealed that TD and TPD markedly reduced tryptophan and tyrosine/phenylalanine levels, respectively. No changes in plasma IL-6 production or ratings of lowered mood were observed, however, subjects did report feeling more fatigued after TD. These findings indicate that a transient disruption in global monoamine function does not stimulate a proinflammatory response of IL-6 in normal volunteers. Copyright © 2002 John Wiley & Sons, Ltd. [source] Histamine induces Toll-like receptor 2 and 4 expression in endothelial cells and enhances sensitivity to Gram-positive and Gram-negative bacterial cell wall componentsIMMUNOLOGY, Issue 2 2004Jaya Talreja Summary Histamine is a major inflammatory molecule released from the mast cell, and is known to activate endothelial cells. However, its ability to modulate endothelial responses to bacterial products has not been evaluated. In this study we determined the ability of histamine to modulate inflammatory responses of endothelial cells to Gram-negative and Gram-positive bacterial cell wall components and assessed the role of Toll-like receptors (TLR) 2 and 4 in the co-operation between histamine and bacterial pathogens. Human umbilical vein endothelial cells (HUVEC) were incubated with lipopolysaccharide (LPS), lipoteichoic acid (LTA), or peptidoglycan (PGN) in the presence or absence of histamine, and the expression and release of interleukin-6 (IL-6), and NF-,B translocation were determined. The effect of histamine on the expression of mRNA and proteins for TLR2 and TLR4 was also evaluated. Incubation of HUVEC with LPS, LTA and PGN resulted in marked enhancement of IL-6 mRNA expression and IL-6 secretion. Histamine alone markedly enhanced IL-6 mRNA expression in HUVEC, but it did not stimulate proportional IL-6 release. When HUVEC were incubated with LPS, LTA, or PGN in the presence of histamine marked amplification of both IL-6 production and mRNA expression was noted. HUVEC constitutively expressed TLR2 and TLR4 mRNA and proteins, and these were further enhanced by histamine. The expression of mRNAs encoding MD-2 and MyD88, the accessory molecules associated with TLR signalling, were unchanged by histamine treatment. These results demonstrate that histamine up-regulates the expression of TLR2 and TLR4 and amplifies endothelial cell inflammatory responses to Gram-negative and Gram-positive bacterial components. [source] Suppression of experimental colitis in mice by CD11c+ dendritic cellsINFLAMMATORY BOWEL DISEASES, Issue 2 2009Joseph E. Qualls PhD Abstract Background: The innate immune system serves a critical role in homeostasis of the gastrointestinal (GI) tract. Both macrophages (MØs) and dendritic cells (DCs) have been shown to have pathogenic roles in animal models of inflammatory bowel disease. However, studies by several labs have established that resident MØs and DCs within the normal GI tract maintain an immunosuppressive phenotype compared to that seen in other peripheral sites. Recent studies by our lab demonstrated that the depletion of both MØs and DCs before the initiation of dextran sodium sulfate (DSS)-induced colitis resulted in exacerbation of disease, partly caused by increased neutrophil influx. Methods/Results: In this current report, DSS-induced colitis was shown to be significantly more severe when DCs were selectively depleted in mice as indicated by changes in weight loss, stool consistency, rectal bleeding, and histopathology. In contrast to enhanced colitis in MØ/DC-depleted mice, which was associated with increased neutrophil influx, increased colitis in DC-depleted mice was not associated with an increase in neutrophils in the colon, as shown by CXCL1 chemokine levels and myeloperoxidase (MPO) activity. However, increased IL-6 gene and protein expression in colon tissues correlated positively with increased colitis severity in DC-depleted mice compared to colitis in DC-intact mice. Conclusions: This study demonstrates that resident DCs can suppress the severity of acute DSS colitis and that regulation of IL-6 production may contribute to DC-mediated control of intestinal inflammation. (Inflamm Bowel Dis 2008) [source] APOE epsilon-4 allele and cytokine production in Alzheimer's diseaseINTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY, Issue 4 2010Paolo Olgiati Abstract Objective The APOE epsilon-4 allele has consistently emerged as a susceptibility factor for Alzheimer's disease (AD). Pro-inflammatory cytokines are detectable at abnormal levels in AD, and are thought to play a pathophysiological role. Animal studies have shown dose-dependent correlations between the number of APOE epsilon-4 alleles and the levels of pro-inflammatory cytokines. The aims of this study were to investigate the influence of APOE genotypes on TNF- ,, IL-6, and IL-1, secreted by peripheral blood mononuclear cells (PBMC) from human patients with AD and to analyze the correlation between cytokine production and AD clinical features. Methods Outpatients with AD (n,=,40) were clinically evaluated for cognitive decline (MMSE) and psychiatric symptoms (Cornell Scale for Depression in Dementia; Neuropsychiatric Inventory) and genotyped for APOE variants. PBMCs were isolated from the donors and used to assess spontaneous and PMA-stimulated secretion of TNF- ,, IL-6, and IL-1,. Cytokine production was determined by immuno-enzymatic assays (ELISA). Results In comparison with their counterparts without APOE4, patients with at least one copy of the APOE epsilon-4 allele showed higher spontaneous (p,=,0.037) and PMA-induced (p,=,0.039) production of IL-1, after controlling for clinical variables. Significant correlations were reported between NPI scores (psychotic symptoms) and IL-6 production. Conclusion These preliminary findings suggest the involvement of inflammatory response in the pathogenic effect of the APOE epsilon-4 allele in AD, although their replication in larger samples is mandatory. The modest correlations between pro-inflammatory cytokines released at peripheral level and AD features emphasizes the need for further research to elucidate the role of neuroinflammation in pathophysiology of AD. Copyright © 2009 John Wiley & Sons, Ltd. [source] Comparison of cytotoxic and inflammatory responses of photoluminescent silicon nanoparticles with silicon micron-sized particles in RAW 264.7 macrophagesJOURNAL OF APPLIED TOXICOLOGY, Issue 1 2009Jonghoon Choi Abstract Photoluminescent silicon nanoparticles have a bright and stable fluorescence and are promising candidates for bio-imaging, cell staining and drug delivery. With increasing development of nanotechnology applications for biomedicine, an understanding of the potential toxicity of nanoparticles is needed to assess safety concerns for clinical applications. The objective of this study was to compare biological responses of silicon nanoparticles (SNs, 3 nm diameter) with silicon microparticles (SMs, ,100,3000 nm diameter) in cultured murine macrophages (RAW 264.7) using standard protocols for assessing cytotoxicity/cell viability and inflammatory responses developed for micron-sized particles. SNs and SMs were exposed to macrophages with and without addition of endotoxin lipopolysaccharide (LPS), a positive inducer of tumor necrosis factor-alpha (TNF- ,), interleukin 6 (IL-6), and nitric oxide (NO). Cytotoxicity was assayed using the dye exclusion and MTT assays. Cell supernatants were assayed for production TNF- ,, IL-6 and NO. SNs at concentrations ,20 µg ml,1 exhibited no cytotoxicity or inflammatory responses; however, SNs and SMs >20 and 200 µg ml,1, respectively, increased cytotoxicity compared with controls. SMs induced concentration-related increases in TNF- , and IL-6 production; in contrast, the production of these cytokines was shown to decrease with increasing concentrations of SNs. NO production was not induced by SNs or SMs alone. Fluorescence microscopy demonstrated that SNs were associated with the macrophages, either internalized or attached to cell membranes. In conclusion, evaluating differences in biological responses for nanoparticles compared with microparticles of the same material may help improve tests to assess biological responses of nanoparticles that may be used in biomedical applications. Copyright © 2008 John Wiley & Sons, Ltd. [source] cAMP activation by PACAP/VIP stimulates IL-6 release and inhibits osteoblastic differentiation through VPAC2 receptor in osteoblastic MC3T3 cellsJOURNAL OF CELLULAR PHYSIOLOGY, Issue 1 2009Azusa Nagata The neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP), a member of the glucagon/vasoactive intestinal peptide (VIP) superfamily, stimulates cyclic AMP accumulation initiating a variety of biological processes such as: neurotropic actions, immune and pituitary function, learning and memory, catecholamine biosynthesis and regulation of cardiopulmonary function. Both osteoclasts and osteoblasts have been shown to express receptors for PACAP/VIP implicated in their role in bone metabolism. To further understand the role of PACAP/VIP family in controlling bone metabolism, we investigated differentiation model of MC3T3-E1 cells, an osteoblastic cell line derived from mouse calvaria. Quantitative RT-PCR analysis demonstrated that MC3T3-E1 cells expressed only VPAC2 receptor and its expression was upregulated during osteoblastic differentiation, whereas VPAC1 and PAC1 receptors were not expressed. Consistent with expression of receptor subtype, both PACAP and VIP stimulate cAMP accumulation in a time- and dose-dependent manner with the similar potency in undifferentiated and differentiated cells, while Maxadilan, a specific agonist for PAC1-R, did not. Furthermore, downregulation of VPAC2-R by siRNA completely blocked cAMP response mediated by PACAP and VIP. Importantly, PACAP/VIP as well as forskolin markedly suppressed the induction of alkaline phosphatase mRNA upon differentiation and the pretreatment with 2,,5,-dideoxyadenosine, a cAMP inhibitor, restored its inhibitory effect of PACAP. We also found that PACAP and VIP stimulated IL-6 release, a stimulator of bone resorption, and VPAC2-R silencing inhibited IL-6 production. Thus, PACAP/VIP can activate adenylate cyclase response and regulate IL-6 release through VPAC2 receptor with profound functional consequences for the inhibition of osteoblastic differentiation in MC3T3-E1 cells. J. Cell. Physiol. 221: 75,83, 2009. © 2009 Wiley-Liss, Inc [source] Influence of progesterone on myometrial contractility in pregnant mice treated with lipopolysaccharideJOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH (ELECTRONIC), Issue 6 2007Hiroshi Anbe Abstract Aim:, To evaluate the effect of progesterone on interleukin (IL)-6, prostaglandin (PG) E2 and nitric oxide (NO) metabolite (NOx) production and contractile activity by NO in pregnant mice treated with lipopolysaccharide (LPS). Methods:, Pregnant C57BL mice on day 14 of gestation were killed 6 h after i.p. injection of LPS (400 ,g/kg) or vehicle. Progesterone (2 mg) was subcutaneously injected 2 h before LPS treatment. Uterine rings were equilibrated in Krebs-Henseleit solution (37°C) bubbled with 20% O2 and 5% CO2 (pH 7.4) for sampling and isometric tension recording. IL-6, PGE2 and NOx productions were measured from the bathing solution. Changes in spontaneous contractile activity in response to cumulative concentrations of l -arginine, diethylamine/nitric oxide (DEA/NO, the NO donor), and 8-bromo-cGMP (8-br-cGMP) were compared. Integral contractile activity over 10 min after each concentration was calculated and expressed as percentage change from basal activity. Statistical analyses were performed using one-way anova followed by Dunnett's test (significance was defined as P < 0.05). Results:, Interleukin-6 (34.7 ± 6.0 pg/g tissue), PGE2 (66.8 ± 6.7 pg/g tissue) and NOx (51.0 ± 5.4 pmol/2 mL/g wet tissue) production were significantly stimulated by LPS treatment (138.2 ± 23.2, 147.0 ± 29.0, 98.6 ± 16.2, respectively; P < 0.05). l -arginine, DEA/NO and 8-br-cGMP concentration-dependently inhibited spontaneous contractions in uterine rings both in LPS-treated and -untreated animals. Treatment with LPS significantly attenuated the maximal inhibition induced by l -arginine, DEA/NO and 8-br-cGMP in uterine rings from pregnant mice. Progesterone significantly decreased the levels of IL-6 production (74.9 ± 12.1, P < 0.05), but not PGE2 and NOx production, and contractile responses by l -arginine, DEA/NO and 8-br-cGMP. Conclusions:, The administration of LPS is associated with increases in IL-6, PGE2 and NO, and these increases may or may not have a role to play in LPS-induced preterm labor. Progesterone reduced the LPS-induced increase in IL-6 production and this may be one of the ways that progesterone reduces the risk of preterm labor. [source] PGE2 and IL-6 production by fibroblasts in response to titanium wear debris particles is mediated through a Cox-2 dependent pathwayJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 1 2004Susan V. Bukata Aseptic loosening of orthopaedic implants is precipitated by wear debris-induced osteolysis. Central to this process are the pro-inflammatory mediators that are produced in response to wear by the fibroblastic cells, which comprise the majority of periprosthetic membranes. Since this pro-inflammatory cascade is mediated by a plethora of factors with redundant functions, it is imperative to establish a hierarchy. Two well-known fibroblast derived pro-inflammatory factors that stimulate wear debris-induced osteoclastic resorption are prostaglandin E2 (PGE2) and IL-6. However, their relationship to each other in this process is poorly defined. Here we show immunohistochemistry of retrieval membranes indicating that COX-2 is the principal cyclooxygenase responsible for PGE2 production in fibroblasts around failed implants. We also performed in vitro experiments with fibroblasts derived from wild-type (WT), COX-1 (,/,) and COX-2 (,/,) mice, which demonstrated that COX-2 is required for Ti wear debris-induced PGE2 production. Interestingly, COX-2 was also required for IL-6 production in these assays, which could be rescued by the addition of exogenous PGE2 (10,6 M). Pharmacology studies that utilized the COX-1 selective inhibitor SC 560, the COX-2 selective inhibitor celecoxib, and the nonselective COX inhibitor indomethacin confirmed these results. Taken together, these results indicate that selective inhibition of prostaglandin signaling could favorably impact aseptic loosening beyond its direct effects on PGE2 synthesis, in that it inhibits downstream pro-inflammatory/pro-osteoclastic cytokine production. © 2003 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved. [source] Prostaglandin F2, upregulates interleukin-6 production in human gingival fibroblastsJOURNAL OF PERIODONTAL RESEARCH, Issue 2 2001Kazuyuki Noguchi Prostaglandin F2,(PGF2,) is a bioactive lipid mediator which has been suggested to be involved in the pathogenesis of periodontal disease. However, the roles of PGF2, in periodontal lesions are poorly understood. In the present study, we investigated the effect of PGF2, on interleukin (IL)-6 production in human gingival fibroblasts (HGF). PGF2,stimulated IL-6 production in a time- and concentration-dependent fashion. IL-1, and tumor necrosis factor ,(TNF,), proinflammatory cytokines, induced IL-6 production in a time-dependent manner, and PGF2,synergistically enhanced IL-6 production induced by IL-1, and TNF,. IL-6 mRNA was expressed in PGF2, -stimulated HGF, and PGF2, increased IL-6 mRNA levels induced by IL-1, and TNF,. Fluprostenol, a selective FP receptor agonist, could mimic PGF2, -induced IL-6 production. Since FP receptors are coupled to elevation of intracellular calcium and activation of protein kinase C (PKC), the mechanism of IL-6 production by PGF2, was investigated using TMB-8, an inhibitor of Ca2+ mobilization from intracellular stores, and calphostin C, an inhibitor of PKC. TMB-8 significantly suppressed PGF2, -induced IL-6 production, whereas calphostin C showed a stimulatory effect on PGF2, -induced IL-6 production. From these data, we suggest that PGF2, upregulates IL-6 production through FP receptors in HGF, that PGF2, synergistically enhances IL-6 production in IL-1,- and TNF,-stimulated HGF, and that PGF2, -induced IL-6 production may be dependent on intracellular Ca2+ mobilization and be downregulated by PKC activation. PGF2, may be involved in the pathogenesis of periodontal disease by enhancing IL-6 levels in periodontal lesions. [source] C5a modulation of interleukin-1, -induced interleukin-6 production by human osteoblast-like cellsJOURNAL OF PERIODONTAL RESEARCH, Issue 3 2000John M. Pobanz Periodontal bone resorption is controlled by osteoblast products, including interleukin (IL)-6, which are stimulated by other cytokines and complement components in the pro-inflammatory milieu. This study demonstrated that human osteoblast-like osteosarcoma cells (MG-63) responded to human recombinant (hr) C5a by releasing significant amounts of the bone-resorbing cytokine IL-6. C5a-induced release of IL-6 was enhanced 330% when cells were exposed to IL-1, prior to C5a challenge at optimal concentrations (1.0 ,g/ml C5a, 0.1 ng/ml IL-1,). Cells simultaneously challenged with these concentrations of C5a and IL-1, produced a 700% increase in IL-6 release relative to cells challenged with IL-1, alone. Incubation of IL-1,-treated cells with anti-human C5a receptor (C5aR) Ab resulted in a 78% suppression of the C5a-induced release of IL-6, but C5aR neutralization did not affect C5a/IL-1, co-stimulation of IL-6. In addition, neither IL-1, nor C5a significantly altered the other's cell-surface receptor relative to binding affinity or density. These results indicate that while MG-63 cells express functional C5aRs, the synergistic effect of C5a and IL-1, on osteoblast IL-6 production is probably controlled by post-receptor signaling events. C5a agonists and antagonist used to alter critical C5a concentrations may present a new point of therapeutic intervention for the treatment of inflammatory bone resorption such as is found in periodontitis. [source] Antimicrobial and anti-inflammatory activity of five Taxandria fragrans oils in vitroMICROBIOLOGY AND IMMUNOLOGY, Issue 11 2008Katherine A. Hammer ABSTRACT The antimicrobial activity of five samples of Taxandria fragrans essential oil was evaluated against a range of Gram-positive (n= 26) and Gram-negative bacteria (n= 39) and yeasts (n= 10). The majority of organisms were inhibited and/or killed at concentrations ranging from 0.06,4.0% v/v. Geometric means of MIC were lowest for oil Z (0.77% v/v), followed by oils X (0.86%), C (1.12%), A (1.23%) and B (1.24%). Despite differences in susceptibility data between oils, oils A and X did not differ when tested at 2% v/v in a time kill assay against Staphylococcus aureus. Cytotoxicity assays using peripheral blood mononuclear cells demonstrated that T. fragrans oil was cytotoxic at 0.004% v/v but not at 0.002%. Exposure to one or more of the oils at concentrations of ,0.002% v/v resulted in a dose responsive reduction in the production of proinflammatory cytokines IL-6 and TNF-,, regulatory cytokine IL-10, Th1 cytokine IFN-, and Th2 cytokines IL-5 and IL-13 by PHA stimulated mononuclear cells. Oil B inhibited the production of all cytokines except IL-10, oil X inhibited TNF-,, IL-6 and IL-10, oil A inhibited TNF-, and IL-6, oil C inhibited IL-5 and IL-6 and oil Z inhibited IL-13 only. IL-6 production was significantly inhibited by the most oils (A, B, C and X), followed by TNF-, (oils A, B and X). In conclusion, T. fragrans oil showed both antimicrobial and anti-inflammatory activity in vitro, however, the clinical relevance of this remains to be determined. [source] Selenium supplementation enhances the protective response to Toxocara canis larvae in micePARASITE IMMUNOLOGY, Issue 8 2008B. PILARCZYK SUMMARY The effect of oral and intraperitoneal supply of sodium selenite on the immune response to, and the course of T. canis larvae infection in mice were determined. The number of worms in the host tissue was reduced but the migratory route of larvae was not affected. Selenite (Se) supplementation influences Se retention in the liver, enhanced IL-5 and eosinophil responses and evoked IL-6 production in mice infected with T. canis. The enhanced protection in mice given Se intraperitoneally was associated with high levels of parasite-specific IgE, and enhanced concentration of Th1-related cytokines such IL-12p70, TNF-, and IFN-,. In mice given Se orally, the predominant cytokines produced were IL-10, MCP-1 and IL-6 and these mice had lower protection. In conclusion, Se supplementation increases production of specific cytokines in mice infected with T. canis and increases protection against infection. [source] Th1 and Th2 cytokine responses to academic stressRESEARCH IN NURSING & HEALTH, Issue 4 2001Duck-Hee Kang Abstract Predominant Th2 profiles are associated with the worsening of asthma, and stress is speculated to induce a Th2 profile. The goals of this study were to examine the responses of the cytokines Th1 (IFN-, and IL-2) and Th2 (IL-4, IL-5, and IL-6) to a stressor and to look at the relationships between cytokine and psychological responses. Twenty-four students with and without a history of asthma completed questionnaires and gave blood samples during nonexam and exam periods. Cytokines were measured by ELISA from supernatants of stimulated mononuclear cells (MNC) and whole blood. During examinations, there were a significant decrease in IL-2 and a significant increase in IL-6 production (both cultures) and a significant decrease in IFN-, production (MNC cultures). Baseline IL-2 levels showed significant negative correlations with several stress and mood scores. Findings of this study indicate a down-regulation of Th1 and a selective up-regulation of Th2 cytokines during a stressful exposure. © 2001 John Wiley & Sons, Inc. Res Nurs Health 24:245,257, 2001 [source] Intracellular glutathione in stretch-induced cytokine release from alveolar type-2 like cellsRESPIROLOGY, Issue 1 2004Behrouz Jafari Objective: Ventilator-induced lung injury (VILI) is characterized by release of inflammatory cytokines, but the mechanisms are not well understood. We hypothesized that stretch-induced cytokine production is dependent on oxidant release and is regulated by intracellular glutathione (GSH) inhibition of nuclear factor ,B (NF-,B) and activator protein-1 (AP-1) binding. Methodology: Type 2-like alveolar epithelial cells (A549) were exposed to cyclic stretch at 15% strain for 4 h at 20 cycles/min with or without N-acetylcysteine (NAC) or glutathione monoethylester (GSH-e) to increase intracellular GSH, or buthionine sulfoximine (BSO), to deplete intracellular GSH. Results: Cyclic stretch initially caused a decline in intracellular GSH and a rise in the levels of isoprostane, a marker of oxidant injury. This was followed by a significant increase in intracellular GSH and a decrease in isoprostane. Stretch-induced IL-8 and IL-6 production were significantly inhibited when intracellular GSH was further increased by NAC or GSH-e (P < 0.0001). Stretch-induced IL-8 and IL-6 production were augmented when intracellular GSH was depleted by BSO (P < 0.0001). NAC blocked stretch-induced NF-,B and AP-1 binding and inhibited IL-8 mRNA expression. Conclusions: We conclude that oxidant release may play a role in lung cell stretch-induced cytokine release, and antioxidants, which increase intracellular GSH, may protect lung cells against stretch-induced injury. [source] ORIGINAL ARTICLE: Antiphospholipid Antibodies Limit Trophoblast Migration by Reducing IL-6 Production and STAT3 ActivityAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 5 2010Melissa J. Mulla Citation Mulla MJ, Myrtolli K, Brosens JJ, Chamley LW, Kwak-Kim JY, Paidas MJ, Abrahams VM. Antiphospholipid antibodies limit trophoblast migration by reducing IL-6 production and STAT3 activity. Am J Reprod Immunol 2010 Problem Women with antiphospholipid antibodies (aPL) are at risk of recurrent miscarriage and pre-eclampsia. aPL target the placenta by binding to ,2 -glycoprotein I (,2 GPI) expressed by the trophoblast. The objective of this study was to evaluate if and how aPL affect first trimester trophoblast migration. Method of study First trimester trophoblast cells were treated with anti-,2 GPI monoclonal antibodies. Migration was determined using a two-chamber assay. Interleukin (IL)-6 production was evaluated by RT-PCR and enzyme-linked immunosorbent assay, and signal transducer and activator of transcription 3 (STAT3) activation was assessed by western blot. Results Trophoblast cells constitutively secreted IL-6 in a time-dependent manner and this directly correlated with STAT3 phosphorylation. In the presence of anti-,2 GPI Abs, trophoblast IL-6 mRNA levels and secretion was downregulated in a Toll-like receptor 4/MyD88-independent manner and this correlated with a reduction in phosphorylated STAT3 levels. In addition, the anti-,2 GPI Abs reduced the migratory potential of trophoblast. Heparin was able to reverse aPL-dependent inhibition of trophoblast IL-6 secretion and migration. Conclusion This study demonstrates that aPL limit trophoblast cell migration by downregulating trophoblast IL-6 secretion and STAT3 activity. As heparin was unable to prevent these effects, our findings may explain why women with antiphospholipid syndrome, treated with heparin, remain at risk of developing obstetrical syndromes, associated with impaired deep placentation, such as pre-eclampsia. [source] ORIGINAL ARTICLE: Endogenous Adenosine Down-Modulates Mid-Trimester IntraAmniotic Tumor Necrosis Factor-, ProductionAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 4 2009Uma Perni Problem, To determine whether adenosine in amniotic fluid down-regulates pro-inflammatory cytokine production. Method of study, Mid-trimester amniotic fluid from 21 women was incubated ex vivo in the presence or absence of human adenosine deaminase, the enzyme that irreversibly degrades adenosine. After 24 hr, supernatants were assayed by ELISA for tumor necrosis factor-, (TNF-,), interleukin (IL)-6, and IL-10. Clinical parameters were obtained after completion of laboratory testing. Results, Inclusion of adenosine deaminase resulted in a median increase in TNF-, production from 0.9 to 7.3 pg/mL (P = 0.0014). IL-6 production exhibited a non-significant median increase from <2.0 to 53.0 pg/mL (P = 0.0780). Median IL-10 production increased slightly from a median of <0.2 to 1.3 pg/mL. Adenosine deaminase-stimulated TNF-, production was proportional to parity and unrelated to gestational age, time of delivery, maternal age or indication for amniocentesis. Conclusion, Adenosine deaminase treatment increases TNF-, production by ex vivo -cultured amniotic fluid. Adenosine contributes to immune modulation in the amniotic cavity. [source] Cytokine Changes in Postmenopausal Women Treated with Estrogens: a Placebo-controlled StudyAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 2 2002GÖRAN BERG PROBLEM:,Hormone replacement therapy (HRT) is being increasingly used in postmenopausal women. Sex steroids are known to affect the immune system in several ways, although this is mainly based on clinical observations and experimental studies. METHOD OF STUDY:,We studied the in vivo effects of transdermal estrogens (50 ,g 17 ,-Estradiol/24 hr) on cytokine production in postmenopausal women. A total of 17 women were randomized to either placebo (n=7) or active estrogen therapy (n=10) for 14 weeks, with addition of oral medoxyprogesterone acetate 10 mg daily during the last 2 weeks in both groups. Secretion of the cytokines IFN-,, IL-4, IL-10 and IL-6 in blood mononuclear cells was determined, spontaneously and after stimulation with common vaccination antigens and mitogen, using the cell ELISA technique. RESULTS:,IL-6 production after stimulation with purified protein derivate (PPD) decreased in the estrogen treated group (P < 0.01). Mitogen-induced IL-6 production was reduced in the estrogen treated group in contrast to an increase in the placebo group, leading to a significant difference (P < 0.01) between the groups after 12 weeks of treatment. This difference was eliminated after an addition of progestagens for 2 weeks. No significant changes were noted for IFN-,, IL-4 or IL-10 in relation to estrogen or placebo treatment. CONCLUSIONS:,In the present controlled study, the main in vivo effect of estrogens was a decrease in IL-6 production, indicating a possible beneficial effect of estrogen therapy. [source] Alteration of Cytokine Production in Follicular Cystic Ovaries Induced in Mice by Neonatal Estradiol InjectionAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 2 2000ROHINI R. DESHPANDE PROBLEM: Neonatal estradiol injections in mice lead to follicular cystic ovaries that are similar to ovaries in patients with polycystic ovarian syndrome (PCOS). The present study examined ovarian cytokine production following neonatal estradiol injection. METHOD OF STUDY: Female (C3H/HeJ×129/HeJ)F1 mice were injected daily with 20 ,g 17,-estradiol from 0,3 days postpartum. At intervals, animals were sacrificed to determine ovarian architecture, circulating levels of estradiol, ovarian and peritoneal machrophage cytokine production, and ovarian P450 aromatase enzyme mRNA levels. RESULTS: Similar to PCOS, our results show that neonatally estradiol-injected mice have lower levels of circulating estrogen that are correlated with decreased mRNA levels of P450 aromatase enzyme. Our data also show that follicular cystic ovaries have increased tumor necrosis factor (TNF)-, and interleukin (IL)-6 production. This increase in TNF-, and IL-6 production is also observed in peritoneal macrophages of estradiol-injected mice. CONCLUSION: The present study showed that neonatal estrogen injection in mice has an overall systemic effect on cytokine production. We speculate that increased cytokine production may alter certain important steps in follicular maturation, ultimately contributing to ovarian dysfunction. [source] Expression of toll-like receptor 3 and toll-like receptor 7 in muscle is characteristic of inflammatory myopathy and is differentially regulated by Th1 and Th17 cytokinesARTHRITIS & RHEUMATISM, Issue 7 2010A. Tournadre Objective To assess the expression of Toll-like receptor 3 (TLR-3) and TLR-7 in muscle tissue from patients with polymyositis (PM) and dermatomyositis (DM) and to investigate the function and regulation of TLR-3 in cultured muscle cells. Methods The expression of TLR-3, TLR-7, HLA class I, and CD56, a marker of immature myoblast precursors, was analyzed using immunohistochemistry. TLR-3 regulation and signaling were assessed in myoblasts and in differentiated myotubes with the TLR-3 agonist poly(I-C), necrotic myoblasts, and Th1 and Th17 cytokines, in the presence or absence of neutralizing anti,TLR-3 antibody. Levels of TLR-3 messenger RNA (mRNA) were quantified by reverse transcription,polymerase chain reaction. Levels of interleukin-6 (IL-6), CCL20, and IL-8 were determined by enzyme-linked immunosorbent assay. Results TLR-3 and TLR-7 were expressed in PM/DM tissues, but not in noninflammatory muscle tissues, and were primarily detected in inflammatory infiltrates, although a few muscle cells were also positive. These TLR-3, and TLR-7,positive fibers expressed high levels of CD56 and HLA class I antigens. A synergy between poly(I-C) and IL-17 was observed for the production of IL-6 and CCL20. Similarly, stimulation with necrotic myoblasts increased IL-6 production, and stimulation with necrotic myoblasts in combination with IL-17 further increased the induction of IL-6. TLR-3 blockade decreased the inducing effect of necrotic myoblasts and IL-17 on IL-6 production. Stimulation with interferon-, (IFN,) increased TLR-3 mRNA levels, but IL-17 down-regulated the inducing effect of IFN,. Conclusion Our findings indicate that TLR-3 and TLR-7 are expressed in inflammatory myopathic tissues, particularly in immature myoblast precursors. Necrotic muscle cells activate cytokine production, in part, through the TLR-3 pathway, with a differential regulatory effect of Th1 and Th17 cytokines. [source] A novel T cell cytokine, secreted osteoclastogenic factor of activated T cells, induces osteoclast formation in a RANKL-independent mannerARTHRITIS & RHEUMATISM, Issue 11 2009Leonard Rifas Objective Chronic T cell activation is central to the etiology of rheumatoid arthritis (RA), an inflammatory autoimmune disease that leads to severe focal bone erosions and generalized systemic osteoporosis. Previous studies have shown novel cytokine-like activities in medium containing activated T cells, characterized by potent induction of the osteoblastic production of interleukin-6 (IL-6), an inflammatory cytokine and stimulator of osteoclastogenesis, as well as induction of an activity that directly stimulates osteoclast formation in a manner independent of the key osteoclastogenic cytokine RANKL. This study was undertaken to identify the factors secreted by T cells that are responsible for these activities. Methods Human T cells were activated using anti-human CD3 and anti-human CD28 antibodies for 72 hours in AIM V serum-free medium to obtain T cell,conditioned medium, followed by concentration and fractionation of the medium by fast-protein liquid chromatography. Biologically active fractions were resolved using sodium dodecyl sulfate,polyacrylamide gel electrophoresis. Major bands were analyzed by mass spectrometry, and a major candidate protein was identified. This novel cytokine was cloned, and its expression was analyzed using recombinant DNA technologies. Results A single novel cytokine that could induce both osteoblastic IL-6 production and functional osteoclast formation in the absence of osteoblasts or RANKL and that was insensitive to the effects of the RANKL inhibitor osteoprotegerin was identified in the activated T cell,conditioned medium; this cytokine was designated secreted osteoclastogenic factor of activated T cells (SOFAT). Further analysis of SOFAT revealed that it was derived from an unusual messenger RNA splice variant coded by the threonine synthase,like 2 gene homolog, which is a conserved gene remnant coding for threonine synthase, an enzyme that functions only in microorganisms and plants. Conclusion SOFAT may act to exacerbate inflammation and/or bone turnover under inflammatory conditions such as RA or periodontitis and in conditions of estrogen deficiency. [source] Interleukin-6 and type I interferon,regulated genes and chemokines mark disease activity in dermatomyositisARTHRITIS & RHEUMATISM, Issue 11 2009Hatice Bilgic Objective Up-regulation of whole blood type I interferon (IFN),driven transcripts and chemokines has been described in a number of autoimmune diseases. An IFN gene expression "signature" is a candidate biomarker in patients with dermatomyositis (DM). This study was performed to evaluate the capacity of IFN-dependent peripheral blood gene and chemokine signatures and levels of proinflammatory cytokines to serve as biomarkers for disease activity in adult and juvenile DM. Methods Peripheral blood samples and clinical data were obtained from 56 patients with adult or juvenile DM. The type I IFN gene signature in the whole blood of patients with DM was defined by determining the expression levels of 3 IFN-regulated genes (IFIT1, G1P2, and IRF7) using quantitative real-time reverse transcription,polymerase chain reaction. Multiplexed immunoassays were used to quantify the serum levels of 4 type I IFN,regulated chemokines (IFN-inducible T cell , chemoattractant, IFN,-inducible 10-kd protein, monocyte chemotactic protein 1 [MCP-1], and MCP-2) and the serum levels of other proinflammatory cytokines, including interleukin-6 (IL-6). Results DM disease activity correlated significantly with the type I IFN gene signature (r = 0.41, P = 0.007) and with the type I IFN chemokine signature (r = 0.61, P < 0.0001). Furthermore, the serum levels of IL-6 were significantly correlated with disease activity (r = 0.45, P = 0.001). In addition, correlations between the serum levels of IL-6 and both the type I IFN gene signature (r = 0.47, P < 0.01) and the type I IFN chemokine signature (r = 0.71, P < 0.0001) were detected in patients with DM. Conclusion These results suggest that serum IL-6 production and the type I IFN gene signature are candidate biomarkers for disease activity in adult and juvenile DM. Coregulation of the expression of IFN-driven chemokines and IL-6 suggests a novel pathogenic linkage in DM. [source] Galectin 3 induces a distinctive pattern of cytokine and chemokine production in rheumatoid synovial fibroblasts via selective signaling pathwaysARTHRITIS & RHEUMATISM, Issue 6 2009Andrew Filer Objective High expression of galectin 3 at sites of joint destruction in rheumatoid arthritis (RA) suggests that galectin 3 plays a role in RA pathogenesis. Previous studies have demonstrated the effects of galectins on immune cells, such as lymphocytes and macrophages. This study was undertaken to investigate the hypothesis that galectin 3 induces proinflammatory effects in RA by modulating the pattern of cytokine and chemokine production in synovial fibroblasts. Methods Matched samples of RA synovial and skin fibroblasts were pretreated with galectin 3 or tumor necrosis factor , (TNF,), and the levels of a panel of cytokines, chemokines, and matrix metalloproteinases (MMPs) were determined using enzyme-linked immunosorbent assays and multiplex assays. Specific inhibitors were used to dissect signaling pathways, which were confirmed by Western blotting and NF-,B activation assay. Results Galectin 3 induced secretion of interleukin-6 (IL-6), granulocyte,macrophage colony-stimulating factor, CXCL8, and MMP-3 in both synovial and skin fibroblasts. By contrast, galectin 3,induced secretion of TNF,, CCL2, CCL3, and CCL5 was significantly greater in synovial fibroblasts than in skin fibroblasts. TNF, blockade ruled out autocrine TNF,-stimulated induction of chemokines. The MAPKs p38, JNK, and ERK were necessary for IL-6 production, but phosphatidylinositol 3-kinase (PI 3-kinase) was required for selective CCL5 induction. NF-,B activation was required for production of both IL-6 and CCL5. Conclusion Our findings indicate that galectin 3 promotes proinflammatory cytokine secretion by tissue fibroblasts. However, galectin 3 induces the production of mononuclear cell,recruiting chemokines uniquely from synovial fibroblasts, but not matched skin fibroblasts, via a PI 3-kinase signaling pathway. These data provide further evidence of the role of synovial fibroblasts in regulating the pattern and persistence of the inflammatory infiltrate in RA and suggest a new and important functional consequence of the observed high expression of galectin 3 in the rheumatoid synovium. [source] Role of placenta growth factor and its receptor flt-1 in rheumatoid inflammation: A link between angiogenesis and inflammationARTHRITIS & RHEUMATISM, Issue 2 2009Seung-Ah Yoo Objective To investigate the direct effects of placenta growth factor (PlGF) and its specific receptor, flt-1, which are known to mediate angiogenesis, on the inflammatory process of rheumatoid arthritis (RA). Methods Expression of PlGF and flt-1 in the synovial tissue of RA patients was examined using immunohistochemistry. Enzyme-linked immunosorbent assay was used to determine the concentrations of PlGF, tumor necrosis factor , (TNF,), and interleukin-6 (IL-6) in culture supernatants of either mononuclear cells or synoviocytes. The flt-1 expression level in mononuclear cells was analyzed by flow cytometry. Experimental arthritis was induced in mice either by immunization with type II collagen (CII) or by injection of anti-CII antibody. Results PlGF was highly expressed in the synovium of RA patients, and its primary source was fibroblast-like synoviocytes (FLS). When stimulated with IL-1,, FLS from RA patients produced higher amounts of PlGF than did FLS from patients with osteoarthritis. Exogenous PlGF specifically increased the production of TNF, and IL-6 in mononuclear cells from RA patients (but not those from healthy controls) via a calcineurin-dependent pathway. The response to PlGF was associated with increased expression of flt-1 on RA monocytes, which could be induced by IL-1, and TNF,. A novel anti,flt-1 hexapeptide, GNQWFI, abrogated the PlGF-induced increase in TNF, and IL-6 production, and also suppressed CII-induced arthritis and serum IL-6 concentrations in mice. Moreover, genetic ablation of PlGF prevented the development of anti-CII antibody,induced arthritis in mice. Conclusion Our data suggest that enhanced expression of PlGF and flt-1 may contribute to rheumatoid inflammation by triggering production of proinflammatory cytokines. The use of the novel anti,flt-1 peptide, GNQWFI, may be an effective strategy for the treatment of RA. [source] Association of interleukin-6 and interleukin-10 genotypes with radiographic damage in rheumatoid arthritis is dependent on autoantibody statusARTHRITIS & RHEUMATISM, Issue 8 2007I. Marinou Objective Recent evidence has highlighted a major genetic contribution to radiographic damage in rheumatoid arthritis (RA). The objective of this study was to determine whether genetic variants in the loci for interleukin-1 (IL-1), IL-6, IL-10, protein tyrosine phosphatase N22 (PTPN22), and selenoprotein S are associated with radiographic damage. Methods Modified Larsen scores of radiographic damage were determined in a cross-sectional population of patients with RA (n = 964). Rheumatoid factor (RF) and anti,cyclic citrullinated peptide (anti-CCP) were also assayed. The Kruskal-Wallis nonparametric test was used to compare median radiographic damage scores across genotype groups, followed by the Cuzick nonparametric test for trend to assess gene-dose effects. Results An allele-dose association of IL-6 ,174G with increasing radiographic damage was present (P = 0.005), but only in patients who were RF positive (P = 0.004) or anti-CCP positive (P = 0.01). Patients with the IL-10 ,592CC genotype had more extensive radiographic damage than did those with the AC or AA genotype (P = 0.006), but this was observed only among patients who were RF negative (P = 0.002) or anti-CCP negative (P = 0.002). However, RF status and anti-CCP status were not associated with the IL-6 or IL-10 genotype. No other genetic associations were detected, apart from a marginal association of PTPN22 +1858T with increased radiographic damage. Conclusion The reported associations of IL-6 ,174G with high IL-6 production and IL-10 ,592 with low IL-10 production and our own results support a role of genetically determined dysregulated cytokine production in disease severity. The lack of association of these genotypes with RF and anti-CCP antibody status suggests that they act downstream of autoantibody production. We conclude that IL-6 and IL-10 genotypes may be useful in predicting disease severity in autoantibody-positive and autoantibody-negative patients, respectively. [source] Selective effects of Lactobacillus casei Shirota on T cell activation, natural killer cell activity and cytokine productionCLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 2 2010H. Dong Summary Modulation of host immunity is an important potential mechanism by which probiotics confer health benefits. This study was designed to investigate the effects of a probiotic strain, Lactobacillus casei Shirota (LcS), on immune function using human peripheral blood mononuclear cells (PBMC) in vitro. In addition, the role of monocytes in LcS-induced immunity was also explored. LcS promoted natural killer (NK) cell activity and preferentially induced expression of CD69 and CD25 on CD8+ and CD56+ subsets in the absence of any other stimulus. LcS also induced production of interleukin (IL)-1,, IL-6, tumour necrosis factor (TNF)-,, IL-12 and IL-10 in the absence of lipopolysaccharide (LPS). In the presence of LPS, LcS enhanced IL-1, production but inhibited LPS-induced IL-10 and IL-6 production, and had no further effect on TNF-, and IL-12 production. Monocyte depletion reduced significantly the impact of LcS on lymphocyte activation, cytokine production and natural killer (NK) cell activity. In conclusion, LcS activated cytotoxic lymphocytes preferentially in both the innate and specific immune systems, which suggests that LcS could potentiate the destruction of infected cells in the body. LcS also induced both proinflammatory and anti-inflammatory cytokine production in the absence of LPS, but in some cases inhibited LPS-induced cytokine production. Monocytes play an important role in LcS-induced immunological responses. [source] Dendritic cells derived from TBP-2-deficient mice are defective in inducing T cell responsesEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 5 2008Aoi Son Abstract Thioredoxin-binding protein-2 (TBP-2), also known as vitamin,D3-up-regulated protein,1 (VDUP1), was identified as an endogenous molecule interacting with thioredoxin (TRX). Here, we show that dendritic cells (DC) derived from TBP-2-deficient mice are defective in the function of T cell activation. To compare TBP-2,/, DC function with wild-type (WT) DC, we stimulated DC with lipopolysaccharide (LPS). Although TBP-2,/, DC and WT DC expressed comparable levels of MHC class,II and costimulatory molecules such as CD40, CD80 and CD86, the IL-12p40, IL-12p70 and IL-6 productions of TBP-2,/, DC were attenuated. In a mixed leukocyte reaction (MLR), the concentrations of IL-2, IFN-,, IL-4 and IL-10 in the culture supernatant of MLR with TBP-2,/, DC were significantly lower than those in the cultures with WT DC. In MLR also, as with LPS stimulation, IL-12p40 and IL-12p70 production from TBP-2,/, DC was less than that from WT DC. Proliferation of T cells cultured with TBP-2,/, DC was poorer than that with WT DC. Invivo delayed-type hypersensitivity responses in TBP-2,/, mice immunized with ovalbumin were significantly reduced compared to WT mice. These results indicate that TBP-2 plays a crucial role in DC to induce T cell responses. [source] | ||||||||||||||||||||||||||||