Effects Of Tranilast And Dexamethasone On Poly(I:C)-induced Inflammatory Molecules Expression By Human Corneal Fibroblasts

Purpose: Viral stromal keratitis is one of the most common causes of blindness.Immunoinflammatory lesions induced by infiltrating immune cells,is the major cause of corneal damage.Polyinosinic-polycytidylic acid [poly(I:C)] can induce the synthesis of various cytokines,chemokines and adhesion molecules in corneal fibroblasts,which is known as an analog of viral double-stranded RNA.The effects of tranilast and dexamethasone on poly(I:C)-induced expression of proinflammatory molecules,as well as the signaling pathways that underlie such effects,were investigated in cultured human corneal fibroblasts.Methods: Human corneal fibroblasts were cultured with poly(I:C)in the presence or absence of tranilast or dexamethasone.Expression of proinflammatory cytokine(IL-6)and chemokines(IL-8 and MCP-1)were analyzed by enzyme-linked immunosorbent analyses(ELISA).Expression of adhesion molecules(ICAM-1 and VCAM-1)and the phosphorylation of mitogen-activated protein kinase(MAPK),c-Jun and NF-?B inhibitory protein(I?B-?)were analyzed by immunoblotting assays.Results: Both tranilast and dexamethasone inhibited the expressions of IL-6,IL-8,MCP-1,ICAM-1 and VCAM-1 by corneal fibroblasts exposed to poly(I:C)in a concentration-dependent manner.Tranilast inhibited the phosphorylation of MAPK JNK and c-Jun,while dexamethasone inhibited the phosphorylation of ERK,P38,JNK,c-Jun and I?B-?.Conclusions: Both tranilast and dexamethasone suppressed poly(I:C)-induced cytokines,chemokines and adhesion molecules expression in human corneal fibroblasts.The inhibitory effects of tranilast were likely mediated by attenuation of Jun-AP-1 signaling,while those of dexamethasone were likely mediated by inhibition of MAPK,AP-1 and NF-?B pathways.Tranilast might therefore be expected as an alternative medicine of dexamethasone to limit immune cell infiltration associated with viral infection of the cornea.