Antagonist of GH-releasing hormone receptors alleviates experimental ocular inflammation
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摘要Disruptions in immunity and occurrence of inflammation cause many eye diseases. The growth hormone-releasing hormone-growth hormone-insulin-like growth factor-1 (GHRH-GH-IGF1) axis exerts regulatory effects on the immune system. Its involvement in ocular inflammation remains to be investigated. Here we studied this signaling in endotoxin-induced uveitis (EIU) generated by LPS. The increase in GHRH receptor (GHRH-R) protein levels was parallel to the increase in mRNA levels of pituitary-specific transcription factor-1, GHRH-R splice variant 1, GHRH, and GH following LPS insult. Elevation of GHRH-R and GH receptor was localized on the epithelium of the iris and ciliary body, and GHRH-R was confined to the infiltrating macrophages and leukocytes in aqueous humor but not to those in stroma. Treatment with GHRH-R antagonist decreased LPS-stimulated surges of GH and IGF1 in aqueous humor and alleviated inflammation by reducing the infiltration of macrophages and leukocytes and the production of TNF-alpha, IL-1 beta, and monocyte chemotactic protein-1. Our results indicate that inflammation in the iris and ciliary body involves the activation of GHRH signaling, which affects the recruitment of immune cells and the production of proinflammatory mediators that contribute to EIU pathogenesis. Moreover, the results suggest that GHRH-R antagonists are potential therapeutic agents for the treatment of acute ocular inflammation.
著者Qin YJ, Chan SO, Chong KKL, Li BFL, Ng TK, Yip YWY, Chen HY, Zhang MZ, Block NL, Cheung HS, Schally AV, Pang CP
期刊名稱Proceedings of the National Academy of Sciences
出版年份2014
月份12
日期23
卷號111
期次51
出版社NATL ACAD SCIENCES
頁次18303 - 18308
國際標準期刊號0027-8424
語言英式英語
關鍵詞experimental uveitis; GHRH analogs; GHRH-GH-IGF1 axis
Web of Science 學科類別Multidisciplinary Sciences; Science & Technology - Other Topics

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