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- Title
PAPep Inhibits Secretion of Poly(I:C)-Induced Inflammatory Cytokines and ICAM-1 Expression in Corneal Fibroblasts by Suppressing the NF-κB/p38 Pathway.
- Authors
Zhu, Shaopin; Xu, Xun; Liu, Kun; Gu, Qing; Wei, Fang; Yang, Xiaolu
- Abstract
<bold>Purpose: </bold>To assess the anti-inflammatory effect and mechanism of a novel peptide, PAPep, in poly(I:C)-stimulated corneal fibroblasts.<bold>Methods: </bold>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.<bold>Results: </bold>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.<bold>Conclusions: </bold>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.
- Subjects
MONOCYTE chemotactic factor; FIBROBLASTS; MITOGEN-activated protein kinases; IMMUNOFLUORESCENCE; MESSENGER RNA; ANTIGENS; CELL culture; CELLULAR signal transduction; COMPARATIVE studies; CORNEA; CYTOKINES; ENZYME-linked immunosorbent assay; RESEARCH methodology; MEDICAL cooperation; NUCLEOTIDES; PEPTIDES; POLYMERASE chain reaction; RESEARCH; TRANSFERASES; DNA-binding proteins; EVALUATION research; CHEMICAL inhibitors
- Publication
Journal of Ocular Pharmacology & Therapeutics, 2018, Vol 34, Issue 5, p395
- ISSN
1080-7683
- Publication type
journal article
- DOI
10.1089/jop.2017.0068