Abstract
Purpose: :
Corneal fibroblasts are connected to each other via gap junctions and contribute to corneal homeostasis. We previously showed that Tumor necrosis factor (TNF)-α, a proinflammatory cytokine, down-regulates connexin43 (Cx43), gap junctional protein, and then inhibits gap-junctional intercellular communication (GJIC) in corneal fibroblasts. The authors examined the role of MAPK signaling pathway in the TNF-α-induced down-regulation of Cx43 in these cells.
Methods: :
Cultured corneal fibroblasts were exposed to TNF-α in the absence or presence of inhibitors of mitogen-activated protein kinase (MAPK) signaling pathways.
Results: :
The effects of TNF-α on Cx43 expression were attenuated by an inhibitor of c-Jun NH2-terminal kinase (JNK inhibitor II) but not by inhibitors of signaling by extracellular signal-regulated kinase (PD98059) or by p38 MAPK (SB203580). JNK inhibitor II also attenuated the inhibitory effect of TNF-α on GJIC and distribution of Cx43.
Conclusions: :
The inhibitory effects of TNF-α on Cx43 expression and GJIC are mediated, at least in part, by the JNK signaling pathway. JNK signaling pathway in corneal fibroblasts may play an important role in corneal inflammation.
Keywords: cornea: stroma and keratocytes • cytokines/chemokines