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Chemokine Release (chemokine + release)
Selected AbstractsInterferon-, differentially modulates the release of cytokines and chemokines in lipopolysaccharide- and pneumococcal cell wall-stimulated mouse microglia and macrophagesEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 11 2002Karl Georg Häusler Abstract During bacterial infections of the CNS, activated microglia could support leucocyte recruitment to the brain through the synthesis of cyto- and chemokines. In turn, invading leucocytes may feedback on microglial cells to influence their chemokine release pattern. Here, we analyzed the capacity of interferon-, (IFN,) to serve as such a leucocyte-to-microglia signal. Production of cyto- and chemokines was stimulated in mouse microglia cultures by treatments with lipopolysaccharide (LPS) from Gram-negative Escherichia coli or cell walls from Gram-positive Streptococcus pneumoniae (PCW). IFN, presence during the stimulation (0.1,100 ng/mL) modulated the patterns of LPS- and PCW-induced cyto- and chemokine release in a dose-dependent, potent and complex manner. While amounts of TNF, and IL-6 remained nearly unchanged, IFN, enhanced the production of IL-12, MCP-1 and RANTES, but attenuated that of KC, MIP-1, and MIP-2. Release modulation was obtained with IFN, preincubation (treatment of cells before LPS or PCW administration), coincubation and even delayed addition to an ongoing LPS or PCW stimulation. Together the changes observed for the microglial chemokine release under IFN, would shift the chemoattractive profile from favouring neutrophils to a preferential attraction of monocytes and T lymphocyte populations , as actually seen during the course of bacterial meningitis. The findings support the view of activated microglia as a major intrinsic source for an instant production of a variety of chemokines and suggest that leucocyte-derived IFN, could potentially regulate the microglial chemokine release pattern. [source] Blockade of IL-15 activity inhibits microglial activation through the NF,B, p38, and ERK1/2 pathways, reducing cytokine and chemokine releaseGLIA, Issue 3 2010Diego Gomez-Nicola Abstract Reactive glia formation is one of the hallmarks of damage to the CNS, but little information exists on the signals that direct its activation. Microglial cells are the main regulators of both innate and adaptative immune responses in the CNS. The proinflammatory cytokine IL-15 is involved in regulating the response of T and B cells, playing a key role in regulating nervous system inflammatory events. We have used a microglial culture model of inflammation induced by LPS and IFN, to evaluate the role of IL-15 in the proinflammatory response. Our results indicate that IL-15 is necessary for the reactive response, its deficiency (IL-15-/-) leading to the development of a defective proinflammatory response. Blockade of IL-15, both with blocking antibodies or with the ganglioside Neurostatin, inhibited the activation of the NF,B pathway, decreasing iNOS expression and NO production. Inhibiting IL-15 signaling also blocked the activation of the mitogen-activated protein kinase (MAPK) pathways ERK1/2 and p38. The major consequence of these inhibitory effects, analyzed using cytokine antibody arrays, was a severe decrease in the production of chemokines, cytokines and growth factors, like CCL17, CCL19, IL-12, or TIMP-1, that are essential for the development of the phenotypic changes of glial activation. In conclusion, activation of the IL-15 system seems a necessarystep for the development of glial reactivity and the regulation of the physiology of glial cells. Modulating IL-15 activity opens the possibility of developing new strategies to control gliotic events upon inflammatory stimulation. © 2009 Wiley-Liss, Inc. [source] The central role of Fas-ligand cell signaling in inflammatory lung diseasesJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 3 2004G. A. DosReis Abstract Following inflammation and injury in the lung, loss of epithelial cell precursors could determine the balance between tissue regeneration and fibrosis. This review discusses evidence that proapoptotic Fas-Fas ligand (FasL) signaling plays a central role in pulmonary inflammation, injury and fibrosis. FasL signaling induces inflammatory apoptosis in epithelial cells and alveolar macrophages, with concomitant IL-1, and chemokine release, leading to neutrophil infiltration. FasL signaling plays a critical role in models of acute lung injury, idiopathic pulmonary fibrosis and silicosis; blockade of Fas-FasL interactions either prevents or attenuates pulmonary inflammation and fibrosis. Serologic and immunohistochemical studies in patients support a major pathogenic role of Fas and FasL molecules in inflammatory lung diseases. Identification of the pathogenic role of FasL could facilitate the discovery of more effective treatments for currently untreatable inflammatory lung diseases. [source] Phytoceuticals: Mighty but ignored weapons against Helicobacter pylori infectionJOURNAL OF DIGESTIVE DISEASES, Issue 3 2008Sun-Young LEE Helicobacter pylori (H. pylori) infection causes peptic ulcer disease, mucosa-associated lymphoid tissue (MALT) lymphomas and gastric adenocarcinomas, for which the pathogenesis of chronic gastric inflammation prevails and provides the pathogenic basis. Since the role of H. pylori infection is promoting carcinogenesis rather than acting as a direct carcinogen, as several publications show, eradication alone cannot be the right answer for preventing H. pylori -associated gastric cancer. Therefore, a non-antimicrobial approach has been suggested to attain microbe-associated cancer prevention through controlling H. pylori -related chronic inflammatory processes and mediators responsible for carcinogenesis. Phytoceutical is a term for plant products that are active on biological systems. Phytoceuticals such as Korean red ginseng, green tea, red wine, flavonoids, broccoli sprouts, garlic, probiotics and flavonoids are known to inhibit H. pylori colonization, decrease gastric inflammation by inhibiting cytokine and chemokine release, and repress precancerous changes by inhibiting nuclear factor-kappa B DNA binding, inducing profuse levels of apoptosis and inhibiting mutagenesis. Even though further unsolved issues are awaited before phytoceuticals are accepted as a standard treatment for H. pylori infection, phytoceuticals can be a mighty weapon for either suppressing or modulating the disease-associated footprints of H. pylori infection. [source] ORIGINAL ARTICLE: Cellular Interaction Regulates Interleukin-8 Secretion by Granulosa-Lutein Cells and Monocytes/MacrophagesAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 1 2009Anna Po Problem, Peri-ovulatory migration of leukocytes towards the follicle plays an important role during corpus luteum formation. In this study, we examined the secretion of the neutrophil chemoattractant interleukin (IL)-8 by ovarian GL cells and the role of monocytes in IL-8 secretion. Method of study, Granulosa-lutein cells were isolated from the pre-ovulatory follicle. After depletion of contaminating leukocytes, GL cells were co-cultured with the myelo-monocytic cell line THP-1. Intracellular IL-8 accumulation, IL-8 secretion, and chemotactic activity of cell culture media were examined. Results, Intracellular IL-8 was predominantly localized in the endoplasmatic reticulum-Golgi both in GL cells and in THP-1 cells. In co-cultured cells, intracellular IL-8-specific immunofluorescence and IL-8 secretion were increased compared with either GL cells or THP-1 cells that were cultured alone. Conditioned cell culture media from GL cells and THP-1 cells induced directed cell migration by neutrophils. Conclusion, Human GL cells constitutively synthesize IL-8. An increased IL-8 secretion by co-cultured GL cells and THP-1 cells suggest that GL cells and monocytes mutually induce chemokine secretion. An initial interaction between GL cells and ovarian leukocytes may therefore contribute to an increased chemokine release and leukocyte recruitment to the forming corpus luteum. [source] CXC and CC chemokines induced in human renal epithelial cells by inflammatory cytokinesAPMIS, Issue 7 2009ELISKA THORBURN (NEE KRASNA) Human renal epithelial cells might play an important role during the allograft rejection by producing chemokines in response to proinflammatory cytokines such as tumor necrosis factor (TNF)-, and interleukin (IL)-1, produced by endothelial and epithelial cells early after transplantation. The production of chemokines allows inflammatory cells to be drawn into the kidney graft and therefore plays a critical role in the pathophysiologic processes that lead to the rejection of renal transplant. In this process, two chemokine superfamilies, the CC and the CXC chemokines, are the most important. The CC chemokines target mainly monocytes and T lymphocytes, while most of the CXC chemokines attract neutrophils. We showed in our study that in vitro, in unstimulated cells, basal mRNA expression of CXC chemokines (Gro,, Gro,, Gro,, ENA-78 and GCP-2, IL-8) that attract neutrophils was detectable and expression of these genes and chemokine release were increased in TNF-,- and IL-1,-induced renal epithelial cells. Most of the CC chemokines [monocyte chemotactic protein-1 (MCP-1), macrophage Inflammatory protein 1 beta (MIP-1,), regulated upon activation, normal T cell expressed and secreted (RANTES) and macrophage inflammatory protein (MIP-3,)] showed detectable mRNA expression only after stimulation with proinflammatory cytokines and not in control cells. TNF-, seems to induce preferably the expression of RANTES, MCP-1, interferon-inducible protein (IP-10) and Interferon-Inducible T-cell Alpha Chemoattractant (I-TAC), while IL-1, induces mainly IL-8 and epithelial neutrophil-activating peptide 78 (ENA-78). [source] Liver X receptor agonism promotes articular inflammation in murine collagen-induced arthritisARTHRITIS & RHEUMATISM, Issue 9 2009Darren L. Asquith Objective Liver X receptors (LXRs) have previously been implicated in the regulation of inflammation and have, in general, been ascribed an antiinflammatory role. This study was therefore undertaken to explore the biologic mechanisms of LXRs in vivo and in vitro in an experimental inflammatory arthritis model. Methods Male DBA/1 mice were immunized with type II collagen and treated from an early or established stage of arthritis with 2 different concentrations of the LXR agonists T1317 and GW3965 or vehicle control. The mice were monitored for articular inflammation and cartilage degradation by scoring for clinical signs of arthritis, histologic examination of the joints, and analysis of serum cytokine and antibody levels. In vitro, primary human monocytes and T cells were cultured in the presence of GW3965 or T1317, and the concentrations of proinflammatory cytokines were measured by multiplex assay. Results Contrary to expectations, LXR agonism with the use of 2 discrete, specific molecular entities led to substantial exacerbation of articular inflammation and cartilage destruction in this murine collagen-induced arthritis model. This was associated ex vivo with elevated cytokine expression, with enhanced Th1 and Th17 cellular responses, and with elevated collagen-specific autoantibody production. In vitro, LXR agonists, in concert with lipopolysaccharide, promoted cytokine and chemokine release from human monocytes, and similar effects were observed in a T cell,macrophage coculture model that closely recapitulates the pathways that drive synovial cytokine release. Conclusion Since LXRs are present in rheumatoid arthritis (RA) synovium, these results suggest that LXR-mediated pathways could exacerbate the chronic inflammatory response typical of RA. [source] The protein kinase C agonist PEP005 increases NF-,B expression, induces differentiation and increases constitutive chemokine release by primary acute myeloid leukaemia cellsBRITISH JOURNAL OF HAEMATOLOGY, Issue 6 2009Astrid Marta Olsnes Summary Acute myeloid leukaemia (AML) cells show constitutive release of several chemokines that occurs in three major clusters: (I) chemokine (C-C motif) ligand (CCL)2,4/chemokine (C-X-C motif) ligand (CXCL)1/8, (II) CCL5/CXCL9,11 and (III) CCL13/17/22/24/CXCL5. Ingenol-3-angelate (PEP005) is an activator of protein kinase C and has antileukaemic and immunostimulatory effects in AML. We investigated primary AML cells derived from 35 unselected patients and determined that PEP005 caused a dose-dependent increase in the release of chemokines from clusters I and II, including several T cell chemotactic chemokines. The release of granulocyte-macrophage colony-stimulating factor and hepatocyte growth factor was also increased. CCL2,4/CXCL1/8 release correlated with nuclear factor (NF)-,B expression in untreated AML cells, and PEP005-induced chemokine production was associated with further increases in the expression of the NF-,B subunits p50, p52 and p65. Increased DNA binding of NF-,B was observed during exposure to PEP005, and the specific NF-,B inhibitor BMS-345541 reduced constitutive chemokine release even in the presence of PEP005. Finally, PEP005 decreased expression of stem cell markers (CD117, CXCR4) and increased lineage-associated CD11b and CD14 expression. To conclude, PEP005 has a unique functional pharmacological profile in human AML. Previous studies have described proapoptotic and T cell stimulatory effects and the present study describes additional T cell chemotactic and differentiation-inducing effects. [source] Changes in IL-8 release and intracellular content in DMSO-differentiated HL-60 cells after treatment with 4-hydroxynonenalCELL BIOCHEMISTRY AND FUNCTION, Issue 5 2008Marina Maggiora Abstract 4-Hydroxynonenal (HNE), a chemotactic aldehyde produced by lipid peroxidation, has been shown to trigger exocytosis in HL-60 cells induced to differentiate toward the granulocytic cell line by DMSO. In this work we studied HNE effects on the intracellular content of IL-8 and its release in DMSO-differentiated HL-60 cells. Cell incubation at 37°C in the presence of 0.1,µM HNE induced a significant increase of IL-8 release after 30,min; the degree of HNE-induced IL-8 secretion became quite strong after 1,h, whereas the intracellular content showed no statistically significant changes. By contrast, 1,µM HNE induced a low decrease of the chemokine release; however, the used HNE concentrations failed to increase the release of lactate dehydrogenase (LDH), a test used to assay cell viability. The addition of 0.1,µM IL-8 to DMSO-differentiated HL-60 cells induced a strong increase of exocytosis, measured by , -glucuronidase secretion. Exocytosis stimulation by IL-8 was much higher than that given by the aldehyde; the addition of various HNE concentrations to cells incubated in the presence of IL-8 decreased the secretion given by the cytokine alone. However, HNE-induced exocytosis was likely to be a direct action of the aldehyde and was not mediated through the stimulation of IL-8 release since HNE was unable to modify IL-8 secretion during the short time of 10,min used in the exocytosis assay. Copyright © 2008 John Wiley & Sons, Ltd. [source] | |||||||||||||