title: Double-stranded RNA induces IL-8 and MCP-1 gene expression via TLR3 in HaCaT-keratinocytes.
abstract: In the present study, we investigated the gene expression of IL-8 and MCP-1 in HaCaT keratinocytes in response to poly(I:C), a synthetic dsRNA analogon. Both gene inductions were found to be mediated by TLR3 and downstream signalling pathways. While poly(I:C) induced IL-8 gene expression was solely inhibited by the NF-κB inhibitor III, MCP-1 gene induction was also blocked by PKA, p38 MAPK and JAK-STAT inhibitors. Moreover, Brefeldin A, an inhibitor of the anterograde transport, suppressed MCP-1 but not IL-8 gene expression, indicating that poly(I:C)-induced cytokines are involved in the chemokine gene expression. Both chemokines were expressed in response to the pro-inflammatory cytokines TNFα and IL-1β; however, MCP-1 gene induction was also found in response to IFNγ. These data are indicative for distinct signalling pathways in the poly(I:C)-induced gene expression of IL-8 and MCP-1 in HaCaT keratinocytes.
authors: University of Witten- Herdecke, Institute of Immunology, Stockumer Stra e 10, D-58453 Witten, Germany. Andreas.Voss@uni-wh.de
authors: Andreas
authors: A
authors: Voss
authors: Gunter
authors: G
authors: Bode
authors: Claus
authors: C
authors: Kerkhoff
mesh_terms: D002460:Cell Line; D018932:Chemokine CCL2 / Q000235:genetics*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics*; D015603:Keratinocytes / Q000187:drug effects / Q000276:immunology*; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D011070:Poly I-C / Q000276:immunology / Q000494:pharmacology; D012330:RNA, Double-Stranded / Q000276:immunology* / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D051196:Toll-Like Receptor 3 / Q000819:agonists / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors
chemical_list: C111835:CCL2 protein, human; D018932:Chemokine CCL2; D004791:Enzyme Inhibitors; D016209:Interleukin-8; D016328:NF-kappa B; D012330:RNA, Double-Stranded; C495344:TLR3 protein, human; D051196:Toll-Like Receptor 3; D017868:Cyclic AMP-Dependent Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D011070:Poly I-C