PAPep Inhibits Secretion of Poly(I:C)-Induced Inflammatory Cytokines and ICAM-1 Expression in Corneal Fibroblasts by Suppressing the NF-κB/p38 Pathway.

PURPOSE: To assess the anti-inflammatory effect and mechanism of a novel peptide, PAPep, in poly(I:C)-stimulated corneal fibroblasts.

METHODS: Corneal fibroblasts were treated with poly(I:C) to elicit inflammation. Real-time polymerase chain reaction (PCR) and ELISA were used to measure the mRNA and protein levels of interleukin (IL)-6, monocyte chemotactic factor (MCP)-1, and interferon gamma (IFN-γ). Real-time PCR, immunofluorescence, and immunoblot were performed to determine ICAM-1 expression. Translocation of NF-κB p65 was observed by immunofluorescence. Phosphorylation of IκBα, NF-κB, and mitogen-activated protein kinase (MAPK) (p38, JNK and ERK) were detected by western blot.

RESULTS: The results showed that PAPep effectively decreased mRNA and protein expression of IL-6, MCP-1, and IFN-γ in corneal fibroblasts exposed to poly(I:C). In addition, PAPep reduced mRNA and protein levels of ICAM-1. The NF-κB and MAPK(p38) pathway were inhibited by PAPep treatment, as indicated by suppression of p65 nuclear translocation, and IκBα, NF-κB, and p38 activation. PAPep showed no effect on JNK or ERK activity.

CONCLUSIONS: PAPep attenuates the expression of inflammatory cytokines and ICAM-1 in corneal fibroblasts induced by poly(I:C) through blocking the NF-κB and MAPK(p38) pathway. PAPep may be considered a promising therapeutic agent for treating viral keratitis.