Cytokine, Chemokine, and Adhesion Molecule Expression Mediated by MAPKs in Human Corneal Fibroblasts Exposed to Poly(I:C)

• DOI: 10.1167/iovs.07-0972
• Publication Date: 2008-07-25T17:35:54Z
• Authors: Yang Liu; Kazuhiro Kimura; Ryoji Yanai; Tai-ichiro Chikama; Teruo Nishida
• Keywords: Proinflammatory cytokine; Intercellular adhesion molecule; Macrophage inflammatory protein

purpose. Polyinosinic-polycytidylic acid [poly(I:C)], an analog of viral double-stranded RNA, interacts with Toll-like receptor (TLR)-3 and thereby elicits immunoinflammatory responses characteristic infection. The effects poly(I:C) on the expression proinflammatory cytokines, chemokines, adhesion molecules, as well signaling pathways that underlie such effects, were investigated in cultured human corneal fibroblasts. methods. Expression molecules intercellular molecule (ICAM)-1 vascular cell (VCAM)-1 was evaluated by immunoblot immunofluorescence analyses. Release cytokine IL-6 chemokines interleukin (IL)-8, granulocyte colony-stimulating factor (G-CSF), macrophage inflammatory protein (MIP)-1β, eotaxin, RANTES measured assay kits. Subcellular localization p65 subunit transcription nuclear (NF-κB) examined analysis. TLR3, phosphorylation (activation) mitogen-activated kinases (MAPKs), degradation NF-κB–inhibitory IκB-α assessed results. Poly(I:C) induced up-regulation release IL-6, IL-8, G-CSF, MIP-1β, RANTES, ICAM-1 VCAM-1 It also activated MAPKs ERK, p38, JNK translocation these cells. Poly(I:C)-induced exotaxin, inhibited differentially MAPK inhibitors PD98059 SB203580 inhibitor II. conclusions. induces MAPK-dependent activation NF-κB Corneal fibroblasts may thus play important role modulation local immune to infection stroma.