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Double-stranded RNA induces IL-8 and MCP-1 gene expression via TLR3 in HaCaT-keratinocytes

: Voss, A.; Bode, G.; Kerkhoff, C.


Inflammation & allergy, drug targets 11 (2012), Nr.5, S.397-405
ISSN: 1871-5281
Fraunhofer IZI ()

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-B 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 TNF and IL-1; however, MCP-1 gene induction was also found in response to IFN. 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.