Cited 0 times in Scipus Cited Count

Pirfenidone attenuates the IL-1β-induced hyaluronic acid increase in orbital fibroblasts from patients with thyroid-associated ophthalmopathy.

Chung, SA  | Jeon, BK | Choi, YH | Back, KO | Lee, JB | Kook, KH
Investigative ophthalmology & visual science, 55(4). : 2276-2283, 2014
Journal Title
Investigative ophthalmology & visual science
PURPOSE: This study aimed to investigate the effect of pirfenidone on the

IL-1beta-induced hyaluronic acid (HA) increase in orbital fibroblasts from

patients with thyroid-associated ophthalmopathy (TAO). METHODS: Primary cultured

orbital fibroblasts were obtained from patients with TAO, and the excreted levels

of HA from IL-1beta-treated cells with or without pirfenidone were measured. The

effect of pirfenidone on IL-1beta-induced hyaluronic acid synthase (HAS)

expression was evaluated. The relevance of the mitogen-activated protein kinase

(MAPK)-mediated signaling pathway in IL-1beta-induced HAS expression was assessed

using specific inhibitors to p38, extracellular signal-regulated kinase (ERK), or

c-Jun N-terminal kinase (JNK). The phosphorylation level of each MAPK in

IL-1beta-treated cells with or without pirfenidone and the level of AP-1 DNA

binding were measured. The inhibitory potency of pirfenidone on HA production was

evaluated using dexamethasone as a reference agent. RESULTS: Pirfenidone strongly

attenuated the IL-1beta-induced HA release in a dose-dependent manner. The

IL-1beta-induced HAS expression was decreased significantly following cotreatment

with pirfenidone at the mRNA and protein levels. The production of mRNAs was

halted by cotreatment with inhibitors of ERK and p38, but not by inhibitors of

JNK. The IL-1beta-induced ERK and p38 phosphorylation, and AP-1 DNA binding were

attenuated in the presence of pirfenidone. Pirfenidone showed greater potency

than dexamethasone in inhibiting increases in IL-1beta-induced HA. CONCLUSIONS:

Pirfenidone attenuates the IL-1beta-induced HA production in orbital fibroblasts

from patients with TAO, at least in part, through suppression of the

MAPK-mediated HAS expression. These results support the potential use of

pirfenidone for treatment of patients with TAO.

Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Ophthalmology
Ajou Authors
국, 경훈  |  정, 승아
Full Text Link
Files in This Item:
There are no files associated with this item.


해당 아이템을 이메일로 공유하기 원하시면 인증을 거치시기 바랍니다.

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.