Double-Stranded RNA Induces IL-8 and MCP-1 Gene Expression via TLR3 in HaCaT-Keratinocytes

Andreas      Voss; Gunter      Bode; Claus      Kerkhoff

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.

Keywords: Cytokine burst, HaCaT keratinocytes, Interleukin 8, monocyte chemotactic protein-1, nonviral dsRNA, toll-like receptor 3, pathogen recognition receptors, proinflammatory cytokines, chemokine, TLR3.