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Chemokine Gene Expression (chemokine + gene_expression)
Selected AbstractsThe chemokines CCL11, CCL20, CCL21, and CCL24 are preferentially expressed in polarized human secondary lymphoid folliclesTHE JOURNAL OF PATHOLOGY, Issue 2 2004Caroline Buri Abstract Chemokines regulate cellular trafficking to and from lymphoid follicles. Here, the distribution pattern of four CCL chemokines is defined by in situ hybridization in human lymphoid follicles from tonsils and lymph nodes (LNs) of newborns and adults. Cells expressing CCL11 (eotaxin) and CCL20 (Exodus) were preferentially located within follicles, while cells expressing CCL21 (secondary lymphoid-tissue chemokine) and CCL24 (eotaxin-2) mRNA were almost exclusively found in the perifollicular areas. Hence, the two CCR3-binding chemokines, CCL11 and CCL24, showed a mutually exclusive expression pattern in the intra- and extra-follicular areas, respectively. Chemokine gene expression paralleled follicular maturation: in tonsils, where approximately 80% of follicles are polarized, CCL11 and CCL20 mRNA-positive cells were detected more frequently than in lymph nodes from adults, where about half of follicles are non-polarized. No intrafollicular chemokine expression was detectable in the primary follicles from newborns. Extrafollicular cells expressing CCL21 and CCL24 were again more frequent in tonsils than in LNs from adults. The observed preferential presence of cells expressing CC chemokines in polarized human lymphoid follicles indicates that chemokines are not only instrumental in the induction of follicle formation, but may also be involved in their further differentiation. Copyright © 2004 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [source] A novel form of NF-,B is induced by Leishmania infection: Involvement in macrophage gene expressionEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 4 2008David Abstract Leishmania spp. are obligate intracellular parasites that inhabit the phagolysosomes of macrophages. Manipulation of host cell signaling pathways and gene expression by Leishmania is critical for Leishmania's survival and resultant pathology. Here, we show that infection of macrophages with Leishmania promastigotes in vitro causes specific cleavage of the NF-,B p65RelA subunit. Cleavage occurs in the cytoplasm and is dependent on the Leishmania protease gp63. The resulting fragment, p35RelA, migrates to the nucleus, where it binds DNA as a heterodimer with NF-,B p50. Importantly, induction of chemokine gene expression (MIP-2/CXCL2, MCP-1/CCL2, MIP-1,/CCL3, MIP-1,/CCL4) by Leishmania is NF-,B dependent, which implies that p35RelA/p50 dimers are able to activate transcription, despite the absence of a recognized transcriptional transactivation domain. NF-,B cleavage was observed following infection with a range of pathogenic species, including L.,donovani, L.,major, L.,mexicana, and L.,(Viannia) braziliensis, but not the non-pathogenic L.,tarentolae or treatment with IFN-,. These results indicate a novel mechanism by which a pathogen can subvert a macrophage's regulatory pathways to alter NF-,B activity. [source] TLR3-mediated signal induces proinflammatory cytokine and chemokine gene expression in astrocytes: Differential signaling mechanisms of TLR3-induced IP-10 and IL-8 gene expressionGLIA, Issue 3 2006Chanhee Park Abstract Viral infection is one of the leading causes of brain encephalitis and meningitis. Recently, it was reported that Toll-like receptor-3 (TLR3) induces a double-stranded RNA (dsRNA)-mediated inflammatory signal in the cells of the innate immune system, and studies suggested that dsRNA may induce inflammation in the central nervous system (CNS) by activating the CNS-resident glial cells. To explore further the connection between dsRNA and inflammation in the CNS, we have studied the effects of dsRNA stimulation in astrocytes. Our results show that the injection of polyinosinic-polycytidylic acid (poly(I:C)), a synthetic dsRNA, into the striatum of the mouse brain induces the activation of astrocytes and the expression of TNF-,, IFN-,, and IP-10. Stimulation with poly(I:C) also induces the expression of these proinflammatory genes in primary astrocytes and in CRT-MG, a human astrocyte cell line. Furthermore, our studies on the intracellular signaling pathways reveal that poly(I:C) stimulation activates I,B kinase (IKK), extracellular signal-regulated kinase (ERK), and c-Jun N-terminal kinase (JNK) in CRT-MG. Pharmacological inhibitors of nuclear factor-,B (NF-,B), JNK, ERK, glycogen synthase kinase-3, (GSK-3,), and dsRNA-activated protein kinase (PKR) inhibit the expression of IL-8 and IP-10 in astrocytes, indicating that the activation of these signaling molecules is required for the TLR3-mediated chemokine gene induction. Interestingly, the inhibition of PI3 kinase suppressed the expression of IP-10, but upregulated the expression of IL-8, suggesting differential roles for PI3 kinase, depending on the target genes. These data suggest that the TLR3 expressed on astrocytes may initiate an inflammatory response upon viral infection in the CNS. © 2005 Wiley-Liss, Inc. [source] Multiple cytokines in human tear specimens in seasonal and chronic allergic eye disease and in conjunctival fibroblast culturesCLINICAL & EXPERIMENTAL ALLERGY, Issue 6 2006A. Leonardi Summary Background Several cytokines are involved in the recruitment and activation of inflammatory cells in ocular allergic diseases. The purpose of the study was to assay multiple cytokines and chemokines in tears, to compare subgroups of allergic conjunctivitis (AC) with controls, and in culture supernatants to determine whether conjunctival fibroblasts produce some of these cytokines. Methods Fifty to one hundred microlitre tears were obtained from patients with active seasonal allergic conjunctivitis (SAC; n=12), vernal keratoconjunctivitis (VKC; n=18), atopic keratoconjunctivitis (AKC; n=6) and non-atopic controls (n=14). Primary conjunctival fibroblasts grown in vitro were stimulated with IL-4, IL-13 or TNF-, for 24 h. Cell-free tear and culture supernatants were assayed for IL-1,, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, IL-13, IFN-,, TNF-,, eotaxin, MCP-1 and RANTES using multiplex bead analysis. Induction of chemokine gene expression was determined by PCR. Results IL-1,, IL-2, IL-5, IL-6, IL-12, IL-13, MCP-1 were increased in all tears groups compared with controls, with highly significant correlations between many of these molecules. In addition IL-4, IFN-,, and IL-10 were elevated in SAC and VKC, while eotaxin and TNF-, were only increased in VKC. IL-6, IL-8, MCP-1, RANTES and eotaxin were detected from fibroblasts cultures, and were all up-regulated by TNF-,. By PCR, fibroblasts expressed MCP-1 transcripts constitutively, whereas IP-10 and Mig were up-regulated by TNF-,. Conclusions Differential cytokine levels support tears as a useful indicator of immune mechanisms occurring during AC. The striking similarities in chemokine profiles between tears and fibroblasts suggest these cells as likely sources of chemokines in tears. [source] Chemokine IL-8 induction by particulate wear debris in osteoblasts is mediated by NF-,BJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 6 2005Elizabeth A. Fritz Abstract Chemokines, or chemotactic cytokines, are major regulators of the inflammatory response and have been identified as pathogenic factors in the periprosthetic soft tissue. Particulate wear debris induced NF-kB activation, the major transcriptional regulator of IL-8 and MCP-1 pro-inflammatory genes and, indeed, both IL-8 and MCP-1 chemokine gene expressions were upregulated in titanium particulate-stimulated human osteoblasts. Here, we demonstrate that phagocytosed particles activate the IL-8 gene promoter via a NF-kB-mediated mechanism. Transfection of a dominant negative mutant IkB, protein that cannot be serine phosphorylated led to suppression of IL-8 promoter activity. The p65/RelA NF-kB subunit activity was affected in both a time- and titanium particle concentration-dependent fashion. Titanium particles led to increased ERK, JNK, and p38 activation in MG-63 osteoblast cells, and IL-8 protein release was suppressed by specific inhibitors of the ERK and p38 MAPK pathways. Together, our results suggest that wear debris particles induce chemokine expression in osteoblasts via NF-kB-mediated transcriptional activation, which is controlled by the MAPK signal transduction pathway. © 2005 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved. [source] | |||||||||||||