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Hyaluronic acid induces COX-2 expression via CD44 in orbital fibroblasts from patients with thyroid-associated ophthalmopathy.

Lim, HS  | Back, KO | Kim, HJ | Choi, YH | Park, YM | Kook, KH
Investigative ophthalmology & visual science, 55(11). : 7441-7450, 2014
Journal Title
Investigative ophthalmology & visual science
PURPOSE: The aim of this study was to determine the effect of hyaluronic acid

(HA) on cyclooxygenase (COX)-2 expression in orbital fibroblasts from patients

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

fibroblasts were obtained from patients with TAO and non-TAO subjects. Dermal and

conjunctival fibroblasts were cultured from the eyelid skin of subjects

undergoing cosmetic lid surgery or cataract surgery, respectively. The cells were

treated with HA and the transcriptional and translational levels of COX-2 were

measured. The expression of CD44 on each type of cells was determined, and the

involvement of CD44 in the HA-induced COX-2 increase in orbital fibroblasts from

patients with TAO was evaluated by using CD44 knockdown cells and by pretreatment

with neutralizing antibody. The relevance of the mitogen-activated protein kinase

(MAPK) or nuclear factor kappa-light-chain-enhancer of activated B cells

(NF-kappaB)-mediated signaling pathway was assessed by immunoblotting for the

phosphorylated form of each MAPK or IkappaB and by using specific inhibitors to

these pathways. RESULTS: Hyaluronic acid increased COX-2 expression in orbital

fibroblasts from patients with TAO, which was not observed in the cells from

non-TAO subjects and conjunctival or dermal fibroblasts. Orbital fibroblasts from

patients with TAO expressed significantly higher level of CD44 than non-TAO

cells, and the increased COX-2 expression by HA in these cells was attenuated by

knockdown or neutralizing of CD44. Hyaluronic acid induced MAPK and IkappaB

phosphorylation; and cotreatment with specific MAPK or NF-kappaB inhibitors

halted HA-induced transcription of COX-2, suggesting the involvement of these

signaling pathways. CONCLUSIONS: Hyaluronic acid induced COX-2 expression in

orbital fibroblasts from patients with TAO via CD44 through the MAPK and

NF-kappaB-mediated signaling pathways. These results suggest that HA may have a

proinflammatory role in the pathogenesis of TAO by inducing COX-2.

Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Ophthalmology
Ajou Authors
국, 경훈  |  임, 헌섭
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