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Pirfenidone attenuates IL-1β-induced COX-2 and PGE2 production in orbital fibroblasts through suppression of NF-K{hooktop}B activity

Title
Pirfenidone attenuates IL-1β-induced COX-2 and PGE2 production in orbital fibroblasts through suppression of NF-K{hooktop}B activity
Authors
Choi Y.-H.Back K.O.Kim H.J.Lee S.Y.Kook K.H.
Ewha Authors
최윤희
SCOPUS Author ID
최윤희scopus
Issue Date
2013
Journal Title
Experimental Eye Research
ISSN
0014-4835JCR Link
Citation
vol. 113, pp. 1 - 8
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
The aim of this study was to determine the effect of pirfenidone on interleukin (IL)-1β-induced cyclooxygenase (COX)-2 and prostaglandin (PG)E2 expression in orbital fibroblasts from patients with thyroid-associated ophthalmopathy (TAO). Primary cultures of orbital fibroblasts from patients with TAO (n = 4) and non-TAO subjects (n = 4) were prepared. The level of PGE2 in orbital fibroblasts treated with IL-1β in the presence or absence of pirfenidone was measured using an enzyme-linked immunosorbent assay. The effect of pirfenidone on IL-1β-induced COX-2 expression in orbital fibroblasts from patients with TAO was evaluated by reverse transcription-polymerase chain reaction (PCR) and quantitative real-time PCR analyses, and verified by Western blot. Activation of nuclear factor-K{hooktop}B (NF-K{hooktop}B) was evaluated by immunoblotting for inhibitor of K{hooktop}B (IK{hooktop}B)α and phosphorylated IK{hooktop}Bα, and DNA-binding activity of p50/p65 NF-K{hooktop}B was analyzed by electrophoretic mobility shift assay. In addition, IL-1 receptor type 1 (IL-1R1) expression was assessed by RT-PCR in IL-1β-treated cells with or without pirfenidone. Pirfenidone significantly attenuated IL-1β-induced PGE2 release in both TAO and non-TAO cells. IL-1β-induced COX-2 mRNA and protein expression decreased significantly following co-treatment with pirfenidone. IL-1β-induced IK{hooktop}Bα phosphorylation and degradation decreased in the presence of pirfenidone and led to decreased nuclear translocation and DNA binding of the active NF-K{hooktop}B complex. In our system, neither IL-1? nor pirfenidone co-treatment influenced IL-1R1 expression. Our results suggest that pirfenidone attenuates the IL-1β-induced PGE2/COX-2 production in TAO orbital fibroblasts, which is related with suppression of the NF-K{hooktop}B activation. © 2013 Elsevier Ltd.
DOI
10.1016/j.exer.2013.05.001
Appears in Collections:
의학전문대학원 > 의학과 > Journal papers
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