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Different Cytokines (different + cytokine)
Selected AbstractsClara cell 10-kDa protein expression in chronic rhinosinusitis and its cytokine-driven regulation in sinonasal mucosaALLERGY, Issue 1 2009Z. Liu Background:, Clara cell 10-kDa protein (CC10) is a multifunction protein with anti-inflammatory and immunomodulatory effects; hence we compared the CC10 expression between chronic rhinosinusitis (CRS) patients with and without nasal polyps (NPs), analyzed its association with disease severity and response to surgery, and explored its regulation via cytokines. Methods:, The plasma and tissue CC10 levels were compared between controls and CRS patients with and without NPs by means of quantitative RT-PCR, ELISA, and immunohistochemistry. Computed tomography (CT) scan and endoscopy findings and symptoms were scored. Nasal explant culture was used to explore the effect of TNF-,, IL-1,, IL-4, INF-,, and IL-10 on CC10 gene regulation. Results:, Compared with controls, the CC10 expression in sinonasal mucosa was significantly inhibited in both CRS patients with and without NPs. There was a significant further decrease of CC10 expression in patients with NPs and asthma. No difference in CC10 plasma levels was found between controls and patients. CC10 levels inversely correlated with preoperative CT scores, and postoperative endoscopy and symptom scores. TNF-,, IL-1, and IL-4 inhibited, whereas INF-, and IL-10 promoted CC10 production in nasal mucosa. A significantly faster decay of CC10 transcripts was seen after IL-1, treatment. IL-1, and IL-10 induced thyroid transcription factor-1 expression. INF-, increased, whereas IL-4 inhibited hepatocyte nuclear factor-3, expression. Conclusion:, CC10 may take part in the pathogenesis of CRS and correlates with disease severity and response to surgery. Different cytokines can regulate CC10 expression in nasal mucosa differentially through modulating mRNA stability and certain transcriptional factors expression. [source] Development of renal bone diseaseEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 2006A. Ferreira Abstract Renal osteodystrophy (ROD) develops as the early stages of chronic renal failure (CRF) and covers a spectrum of bone changes observed in the uraemic patient, which extend from high remodelling bone disease (frequently known as osteitis fibrosa) to low turnover, or adynamic disease. Between these two extremes there are also cases of bone mineralization compromised in variable degrees, as is the case of ,mixed bone disease' and osteomalacia. The dynamic process of bone remodelling is compromised in CRF, and a positive or negative bone balance can be observed in uraemic patients. In addition to the classic modulators of bone remodelling, like parathyroid hormone, calcitriol and calcitonin, other factors were recently identified as significant modulators of osteoblast and osteoclast activation in uraemic patients. In fact, different cytokines and growth factors, acting at an autocrine or paracrine level, seem to play a relevant role in the bone and mineral changes observed in uraemia. Recently, observations have been made of the development of more sensitive and specific techniques to assay different biochemical markers of bone turnover and mineral metabolism. Analogously, new contributions of conventional bone histology, bone immunocytochemistry and molecular biology, which enabled the understanding of some etiopathogenic mechanisms of ROD, were observed. [source] Induction of systemic TNF, in Natalizumab-treated multiple sclerosisEUROPEAN JOURNAL OF NEUROLOGY, Issue 3 2008M. Khademi The mRNA expression of eight different cytokines in peripheral blood mononuclear cells in 19 individuals with multiple sclerosis was determined at baseline and after 6 months of open-label treatment with natalizumab. Cellular expression of tumor necrosis factor , (TNF,) mRNA and number of cells secreting TNF, and interferon , protein significantly increased over the 6 months. Kurtzke EDSS scores improved because of the resolution of relapses, but not fatigue severity scores. The observed increases in systemic proinflammatory cytokines by natalizumab treatment are discussed in relation to fatigue and systemic immunity. [source] Neuron,Glia Signaling in Trigeminal Ganglion: Implications for Migraine PathologyHEADACHE, Issue 7 2007Srikanth Thalakoti BS Objective.,The goal of this study was to investigate neuronal,glial cell signaling in trigeminal ganglia under basal and inflammatory conditions using an in vivo model of trigeminal nerve activation. Background.,Activation of trigeminal ganglion nerves and release of calcitonin gene-related peptide (CGRP) are implicated in the pathology of migraine. Cell bodies of trigeminal neurons reside in the ganglion in close association with glial cells. Neuron,glia interactions are involved in all stages of inflammation and pain associated with several central nervous system (CNS) diseases. However, the role of neuron,glia interactions within the trigeminal ganglion under normal and inflammatory conditions is not known. Methods.,Sprague,Dawley rats were utilized to study neuron,glia signaling in the trigeminal ganglion. Initially, True Blue was used as a retrograde tracer to localize neuronal cell bodies in the ganglion by fluorescent microscopy and multiple image alignment. Dye-coupling studies were conducted under basal conditions and in response to capsaicin injection into the TMJ capsule. S100B and p38 expression in neurons and glia were determined by immunohistochemistry following chemical stimulation. CGRP levels in the ganglion were measured by radioimmunoassay in response to capsaicin. In addition, the effect of CGRP on the release of 19 different cytokines from cultured glial cells was investigated by protein microarray analysis. Results.,In unstimulated control animals, True Blue was detected primarily in neuronal cell bodies localized in clusters within the ganglion corresponding to the V3 region (TMJ capsule), V2 region (whisker pad), or V1 region (eyebrow and eye). However, True Blue was detected in both neuronal cell bodies and adjacent glia in the V3 region of the ganglion obtained from animals injected with capsaicin. Dye movement into the surrounding glia correlated with the time after capsaicin injection. Chemical stimulation of V3 trigeminal nerves was found to increase the expression of the inflammatory proteins S100B and p38 in both neurons and glia within the V3 region. Unexpectedly, increased levels of these proteins were also observed in the V2 and V1 regions of the ganglion. CGRP and the vesicle docking protein SNAP-25 were colocalized in many neuronal cell bodies and processes. Decreased CGRP levels in the ganglion were observed 2 hours following capsaicin stimulation. Using protein microarray analysis, CGRP was shown to differentially regulate cytokine secretion from cultured trigeminal ganglion glia. Conclusions.,We demonstrated that activation of trigeminal neurons leads to changes in adjacent glia that involve communication through gap junctions and paracrine signaling. This is the first evidence, to our knowledge, of neuron,glia signaling via gap junctions within the trigeminal ganglion. Based on our findings, it is likely that neuronal,glial communication via gap junctions and paracrine signaling are involved in the development of peripheral sensitization within the trigeminal ganglion and, thus, are likely to play an important role in the initiation of migraine. Furthermore, we propose that propagation of inflammatory signals within the ganglion may help to explain commonly reported symptoms of comorbid conditions associated with migraine. [source] CCR5 deficiency exacerbates T-cell,mediated hepatitis in mice,HEPATOLOGY, Issue 4 2005Christophe Moreno Experimental T-cell,mediated hepatitis induced by concanavalin A (Con A) involves the production of different cytokines and chemokines and is characterized by leukocyte infiltration. Because the chemokine receptor CCR5 and its ligands (CCL3, CCL4, and CCL5) regulate leukocyte chemotaxis and activation, we investigated the role of CCR5 during Con A,induced liver injury. Serum levels of CCR5 ligands and their hepatic transcript levels were significantly increased after Con A injection, whereas CCR5+ liver mononuclear cells were recruited to the liver. CCR5-deficient (CCR5,/,) mice disclosed increased mortality and liver injury following Con A administration compared with wild-type mice. CCR5,/, mice also exhibited increased production of interleukin 4, tumor necrosis factor ,, CCL3, CCL4, and CCL5, and a prominent liver mononuclear cell infiltrate, among which many cells were CCR1+. In vivo neutralization of CCR5 ligands in CCR5,/, mice afforded a protection against hepatitis only when CCL5 was neutralized. In conclusion, CCR5 deficiency exacerbates T-cell,mediated hepatitis, and leads to increased levels of CCR5 ligands and a more pronounced liver mononuclear infiltrate, suggesting that CCR5 expression can modulate severity of immunomediated liver injury. (HEPATOLOGY 2005;42:854,862.) [source] Host's innate immune response to fungal and bacterial agents in vitro: up-regulation of interleukin-15 gene expression resulting in enhanced natural killer cell activityIMMUNOLOGY, Issue 2 2003Phay Tran Summary Natural killer (NK) cells play an important role in the first line of defence against viral infections. We have shown earlier that exposure of human peripheral blood mononuclear cells (PBMC) to viruses results in rapid up-regulation of NK cell activity via interleukin-15 (IL-15) induction, and that this mechanism curtails viral infection in vitro. By using Candida albicans, Escherichia coli and Staphylococcus aureus, we now show here that exposure of PBMC to fungi and bacteria also results in an immediate increase of NK cytotoxicity. Reverse transcriptase,polymerase chain reaction and Western blot analyses as well as the use of antibodies against different cytokines revealed that IL-15 induction played a predominant role in this NK activation. These results indicate that IL-15 is also involved in the innate immune response against fungal and bacterial agents. [source] Enhanced efficacy of DNA vaccination against Her-2/neu tumor antigen by genetic adjuvantsINTERNATIONAL JOURNAL OF CANCER, Issue 1 2004Sun Young Chang Abstract Certain types of malignant tumors overexpress Her-2/neu, a transmembrane glycoprotein of the class I receptor tyrosine kinase erbB family. To develop an effective Her-2/neu vaccine for selective immunotherapy of these malignancies, we prepared Her-2/neu DNA plasmid encoding the transmembrane and extracellular domain (pHM) and tested the ability of this construct to induce antitumor immunity in animal models. In addition, we investigated the effects of cytokine used as a genetic adjuvant. Modulation by factors that affect T-cell function or hematopoiesis, including interleukin-12, interleukin-15, interleukin-18, interleukin-23, Eta-1, Flt3L and GM-CSF, was studied in the forms of monocistronic and bicistronic plasmid. Our results demonstrated that vaccination of pHM could induce successful antitumor immunity against Her-2/neu-expressing murine tumor cells in BALB/c mice. We also showed that the antitumor activity of pHM was augmented by coadministration and coexpression of different cytokines. Despite the similar levels of gene expression, the antitumor effects of bicistronic plasmids coexpressing Her-2/neu antigen and cytokine were improved in comparison with coadministration of separate monocistronic plasmid. In particular, coexpression of interleukin-18 or GM-CSF with Her-2/neu increased antitumor activity in both preventive and therapeutic experiments. These findings can help in the decision concerning which of the various cytokine adjuvants should be used for the development of a Her-2/neu DNA vaccine. In addition, our results from a large panel of cytokine adjuvants in the various tumor models may provide an insight into the important immune components of antitumor immunity. © 2004 Wiley-Liss, Inc. [source] Analyzing cell fate control by cytokines through continuous single cell biochemistryJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 2 2009Michael A. Rieger Abstract Cytokines are important regulators of cell fates with high clinical and commercial relevance. However, despite decades of intense academic and industrial research, it proved surprisingly difficult to describe the biological functions of cytokines in a precise and comprehensive manner. The exact analysis of cytokine biology is complicated by the fact that individual cytokines control many different cell fates and activate a multitude of intracellular signaling pathways. Moreover, although activating different molecular programs, different cytokines can be redundant in their biological effects. In addition, cytokines with different biological effects can activate overlapping signaling pathways. This prospect article will outline the necessity of continuous single cell biochemistry to unravel the biological functions of molecular cytokine signaling. It focuses on potentials and limitations of recent technical developments in fluorescent time-lapse imaging and single cell tracking allowing constant long-term observation of molecules and behavior of single cells. J. Cell. Biochem. 108: 343,352, 2009. © 2009 Wiley-Liss, Inc. [source] IL-1, and PGE2 levels are increased in the saliva of children with Langerhans cell histiocytosisJOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 9 2008Virginia F. Preliasco Langerhans cell histiocytosis (LCH) is a rare disorder mainly of children, whose pathogenesis is still unknown. Some studies have demonstrated that LCH lesions produce different cytokines abnormally that may be relevant to the pathogenesis of the disease. The purpose of this study was to investigate interleukin-1, (IL-1,) and prostaglandin E2 (PGE2) levels in saliva from children with different clinical subtypes of LCH. We studied 29 children with LCH: seven unifocal (Group I), seven multifocal (Group II), 15 multisystemic (Group III) and 12 healthy volunteers (Group IV). Salivary IL-1, and PGE2 levels were significantly higher in LCH than in normal children. A multi-comparison test showed significantly (P < 0.001) higher levels of both IL-1, and PGE2 in saliva from Group III compared with Groups II and I. A significant correlation (r = 0.05) between IL-1, and PGE2 concentrations in saliva from each group was determined. Our findings demonstrated an association between high concentrations of salivary IL-1, and PGE2 and advanced stages of the disease. This allows us to suggest that the abnormal amount of these factors in saliva may serve as a risk marker for disease progression. [source] SCHWANN CELL APOPTOSIS IN TISSUE CULTURE FOLLOWING THE ADMINISTRATION OF PRO-INFLAMMATORY CYTOKINESJOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 1 2000E. Scarpini In immune-mediated demyelination of the nervous system, glial cell apoptosis has been observed recently; however, the relevance of the phenomenon and the characterization of the involved molecules are still controversial. Cytokines are secreted by many cells, including inflammatory and glial cells, and appear to play a relevant role in the peripheral nervous system (PNS) immuno-mediated demyelination, being active in promoting the damage to Schwann cells, myelin, and axons. Even though the exact role of the different cytokines is at present uncertain, they have a sequential different expression in PNS immune-mediated demyelination and could induce apoptotic death of Schwann cells in the vicinity of the inflammatory reaction via the expression of CD95 (Apo1/Fas). This study has been designed to detect in rat primary Schwann cell tissue cultures whether the administration of IL-1B and IFN-y can induce cell death. Identification of apoptotic Schwann cell was performed by morphological, immunohistochemical, and electron-microscopy analysis. Our results show that Schwann cells stimulated by proinflammatory cytokines IL-1B and IFN-y show morphological evidence of nuclear chromatin condesation at the DAPI staining and are TUNEL positive. The same features of apoptotic cell death were observed by electron microscopy. These findings provide evidence to support the hypothesis that cytokines can directly damage Schwann cells in disorders of the PNS. [source] TG101209, a novel JAK2 inhibitor, has significant in vitro activity in multiple myeloma and displays preferential cytotoxicity for CD45+ myeloma cells,AMERICAN JOURNAL OF HEMATOLOGY, Issue 9 2010Vijay Ramakrishnan Interaction of myeloma cells with the bone marrow microenvironment is mediated in large part through different cytokines, especially VEGF and IL6. These cytokines, especially IL6, leads to upregulation of the JAK/STAT pathway in myeloma cell, contributing to increased proliferation, decreased apoptosis, and acquired drug resistance. Here, we examined the preclinical activity of a novel JAK2 inhibitor TG101209. TG101209 induced dose- and time-dependent cytotoxicity in a variety of multiple myeloma (MM) cell lines. The induction of cytotoxicity was associated with inhibition of cell cycle progression and induction of apoptosis in myeloma cell lines and patient-derived plasma cells. Evaluation of U266 cell lines and patient cells, which have a mix of CD45 positive and negative cells, demonstrated more profound cytotoxicity and antiproliferative activity of the drug on the CD45+ population relative to the CD45, cells. Exploring the mechanism of action of TG101209 indicated downregulation of pJak2, pStat3, and Bcl-xl levels with upregulation of pErk and pAkt levels indicating cross talk between signaling pathways. TG101209, when used in combination with the PI3K inhibitor LY294002, demonstrated synergistic cytotoxicity against myeloma cells. Our results provide the rationale for clinical evaluation of TG101209 alone or in combination with PI3K/Akt inhibitors in MM. Am. J. Hematol., 2010. © 2010 Wiley-Liss, Inc. [source] 3364: Cytokines in enucleated eyesACTA OPHTHALMOLOGICA, Issue 2010MJ JAGER Purpose One of the prognostically bad parameters in uveal melanoma is the presence of an inflammatory phenotype, characterized by an increased expression of HLA antigens and an immunologic infiltrate. We wondered whether the presence of specific chemokines and cytokines in the aqueous humor (AqH) from uveal melanoma-containing eyes is associated with this inflammatory phenotype, with the presence of macrophages, and/or with survival. Methods Directly following enucleation, AqH was obtained from 37 eyes containing uveal melanoma. Samples were stored at -80 °C till use. Using a multiplex bead array, 15 different cytokines were measured. Determination of intratumoral macrophages was performed by immunohistochemistry and immunofluorescence. The presence of specific cytokines was compared to histopathological, genetic and clinical tumor characteristics, as well as patient survival. Results Several cytokines showed a significantly higher expression in the AqH from uveal melanoma-containing eyes compared to the AqH from eyes undergoing cataract surgery. Only MCP-3 was associated with the presence of macrophages and the tumor promoting M2-type macrophage in uveal melanoma patients. Hardly any correlations were found between cytokine levels and known prognostic factors for uveal melanoma. Also, cytokine levels were not of predictive value for survival. Conclusion Although increased levels of inflammation-related cytokines are present in the AqH of uveal melanoma-containing eyes, hardly any associations with the presence of macrophages and their subtypes, with clinical and histopathological parameters, and prognosis were found. [source] Chronic rhinosinusitis with and without nasal polyps is associated with decreased expression of glucocorticoid-induced leucine zipperCLINICAL & EXPERIMENTAL ALLERGY, Issue 5 2009X-H. Zhang Summary Background Chronic rhinosinusitis without nasal polyps (CRSsNP) and with nasal polyps (CRSwNP) is characterized by persistent inflammation of sinonasal mucosa. Glucocorticoid-induced leucine zipper (GILZ) is a recently described anti-inflammatory mediator. Objective Here we analysed the expression of GILZ in CRSsNP and CRSwNP, its association with response to surgery, and its cytokine-driven expression regulation in the upper airways. Methods The messenger RNA (mRNA) and protein expression of GILZ in 33 CRSsNP, 32 CRSwNP, and 11 control samples was assessed by means of a quantitative RT-PCR and immunohistochemistry, respectively. Nasal explant culture was used to investigate the effect of IFN-,, IL-4, IL-13, IL-1,, and TNF-, on GILZ mRNA expression in normal sinonasal mucosa. Results The GILZ mRNA and protein expression was significantly suppressed in both CRSsNP and CRSwNP patients compared with controls. No significant difference in GILZ expression was found between CRSsNP and CRSwNP patients. Comparing patients responsive and patients recalcitrant to surgery, a significant further decrease of GILZ expression was found in recalcitrant patients both in the CRSsNP and in the CRSwNP group. IL-1,, TNF-,, IL-4, and IL-13 reduced, whereas IFN-, enhanced GILZ mRNA levels in the sinonasal mucosa. Conclusion Down-regulated expression of GILZ may contribute to the pathogenesis of CRSsNP and CRSwNP and associate with response to surgery. GILZ expression in the upper airways can be regulated differentially by different cytokines. [source] Circulating ,/, T lymphocytes from systemic sclerosis (SSc) patients display a T helper (Th) 1 polarizationCLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 2 2001R. Giacomelli Systemic sclerosis (SSc) is a connective tissue disease in which immune system activation is evidenced by high levels of different cytokines in the sera and/or in the supernatants of cultured peripheral blood mononuclear cells (PBMC) and by the presence of specific autoantibodies. ,/, T cells accumulate in the lung and the skin of SSc patients suggesting their potential role in the development and maintenance of the disease. The aim of this study was to assess cytokine production and cytotoxic activity of circulating ,/, T lymphocytes obtained from SSc patients and to evaluate their potential role during this disorder. Our results showed that both the proportion and the absolute number of IFN- ,,/, -producing cells (i.e. displaying a Th1 polarization) in SSc was significantly higher than either the proportion and the absolute number of IL-4 ,/, -producing cells in SSc or the proportion and the absolute number of IFN- ,,/, -producing cells in healthy controls (P < 0·05 for both groups). Furthermore, the cytotoxic activity of enriched ,/, T cells was significantly increased in SSc patients compared with controls. The results concerning the V,1+ T cell subset paralleled those of total ,/, T lymphocytes. In contrast, ,/, T cells from SSc and control subjects displayed Th2 cytokine production. All these findings were independent of both disease subset and clinical status. Our data demonstrate that, although SSc is generally considered a Th2 autoimmune disease, Th1 polarization of ,/, T cells and an increase in their cytotoxic activity is observed in SSc, suggesting that ,/, T cells could have a relatively autonomous role in the pathogenesis in this disease. [source] | ||||||||||||||||||||||