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

作者：Zhu, Shaopin; Xu, Xun; Liu, Kun; Gu, Qing; Wei, Fang; Yang, Xiaolu^*

来源：Journal of Ocular Pharmacology and Therapeutics, 2018, 34(5): 395-402.

DOI：10.1089/jop.2017.0068

• peptide
• poly(I:C)
• corneal inflammation
• corneal fibroblasts
• ICAM-1

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-). Real-time PCR, immunofluorescence, and immunoblot were performed to determine ICAM-1 expression. Translocation of NF-B p65 was observed by immunofluorescence. Phosphorylation of IB, NF-B, 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- in corneal fibroblasts exposed to poly(I:C). In addition, PAPep reduced mRNA and protein levels of ICAM-1. The NF-B and MAPK(p38) pathway were inhibited by PAPep treatment, as indicated by suppression of p65 nuclear translocation, and IB, NF-B, 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-B and MAPK(p38) pathway. PAPep may be considered a promising therapeutic agent for treating viral keratitis.

• 出版日期2018-6
• 单位上海交通大学