期刊
CURRENT EYE RESEARCH
卷 35, 期 2, 页码 165-175出版社
TAYLOR & FRANCIS INC
DOI: 10.3109/02713680903453494
关键词
Animal model; DA-6034; Dry eye; Inflammatory cytokine; MAPK signaling pathway
资金
- Ministry of Health, Welfare and Family Affairs, Republic of Korea [A084800]
- Korea Health Promotion Institute [A084800] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
Purpose: To investigate the effect of DA-6034, 7-carboxymethyloxy-3', 4', 5-trimethoxy flavone, in experimentally-induced inflammatory dry eye in rabbit. In addition, to elucidate the mechanism of DA-6034, we evaluated the mitogen-activated protein kinase ( MAPK) signaling pathway and transcriptional factor-kappa B (NF-kB) in corneal epithelial cells. Methods: Rabbit lacrimal glands were injected with the T-cell mitogen concanavalin A (Con A). DA-6034 was then administered topically four times a day for six days starting 24 hr after Con A injection. Tear volume, tear function, MMP-9 and inflammatory cytokine levels in the lacrimal glands, and histological evaluation were subsequently assessed. In in vitro study, phosphorylated MAPKs (c-Jun NH2-terminal kinase (JNK) and p38 MAPK) and NF-kB were detected by enzyme-linked immunosorbent assay (ELISA) using human corneal epithelial cells. Results: A single injection of Con A into the lacrimal glands induced a pronounced inflammatory response, caused elevated levels of MMP-9 and cytokines IL-8 and TGF-beta(1), and induced a decrease in tear volume and shortening of tear breakup time (TBUT). In this inflammation model of dry eye, DA-6034 clearly showed therapeutic efficacy by restoring tear function and inhibiting inflammatory responses after topical ocular application. Furthermore, DA-6034 attenuated the phosphorylation of JNK and p38 MAPK and inhibited NF-kB activation in a concentration-dependent manner in corneal epithelial cells. Conclusions: These results suggest that DA-6034 has the therapeutic effect in rabbit lacrimal gland inflammation model of dry eye and might be a potential treatment option for acute dry eye syndrome.
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