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Pirfenidone inhibits the induction of COX‐2 stimulated by IL‐1β at a step of NF‐κB DNA binding in orbital fibroblast
Author(s) -
KOOK K,
PARK S,
CHOI A
Publication year - 2012
Publication title -
acta ophthalmologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.534
H-Index - 87
eISSN - 1755-3768
pISSN - 1755-375X
DOI - 10.1111/j.1755-3768.2012.t002.x
Subject(s) - pirfenidone , p50 , prostaglandin e2 , fibroblast , medicine , cyclooxygenase , dna damage , dna , cancer research , pharmacology , chemistry , microbiology and biotechnology , gene , transcription factor , biochemistry , in vitro , enzyme , biology , idiopathic pulmonary fibrosis , lung
Purpose The aim of this study was to determine the effect of pirfenidone on interleukin‐1β(IL‐1β)‐induced cyclooxygenase 2(COX‐2) increase in orbital fibroblasts from patients with thyroid‐associated ophthalmopathy(TAO). Methods Orbital fat tissues were obtained during decompression surgery of patients with TAO and orbital fibroblasts were primarily cultured. After treatment of cells with IL‐1β in the presence and absence of pirfenidone, COX‐2 induction and its signal including NF‐κB were analyzed. The effect of pirfenidone on the IL‐1β‐induced prostaglandin E2(PGE2) production in orbital fibroblast was also evaluated. Results Pirfenidone attenuated the IL‐1β‐induced COX‐2 mRNA and protein increase. In electrophoric mobility shift assay, pirfenidone showed the inhibitory effect on NF‐κB DNA binding. However, pirfenidone showed no effect on the degradation and phosphorylation of IκB, and could not prevent nuclear translocation of p50/p65. Finally, the production of PGE2 was nicely inhibited by pirfenidone. Conclusion The results of this study indicate that pirfenidone effectively attenuates IL‐1β‐induced COX‐2 gene expression at a step of NF‐κB DNA binding, which suggests that pirfenidone could be considered as a candidate for treatment of thyroid‐associated ophthalmopathy.