Antagonist of GH-releasing hormone receptors alleviates experimental ocular inflammation

Yong Jie Qin, Sun On Chan, Kelvin Kam Lung Chong, Benjamin Fuk Loi Li, Tsz Kin Ng, Yolanda Wong Ying Yip, Haoyu Chen, Mingzhi Zhang, Norman L Block, Herman S Cheung, Andrew V Schally, Chi Pui Pang

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

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 epitheliumof 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-α, IL-1β, 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.

Original languageEnglish
Pages (from-to)18303-18308
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume111
Issue number51
DOIs
StatePublished - Dec 23 2014

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Hormones
Inflammation
Ciliary Body
Aqueous Humor
Uveitis
Iris
Endotoxins
Leukocytes
Macrophages
Growth Hormone-Releasing Hormone
Eye Diseases
Chemokine CCL2
Somatomedins
Interleukin-1
Growth Hormone
somatotropin releasing hormone receptor
Immune System
Immunity
Transcription Factors
Messenger RNA

Keywords

  • Experimental uveitis
  • GHRH analogs
  • GHRH-GH-IGF1 axis

ASJC Scopus subject areas

  • General

Cite this

Antagonist of GH-releasing hormone receptors alleviates experimental ocular inflammation. / Qin, Yong Jie; Chan, Sun On; Chong, Kelvin Kam Lung; Li, Benjamin Fuk Loi; Ng, Tsz Kin; Yip, Yolanda Wong Ying; Chen, Haoyu; Zhang, Mingzhi; Block, Norman L; Cheung, Herman S; Schally, Andrew V; Pang, Chi Pui.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 111, No. 51, 23.12.2014, p. 18303-18308.

Research output: Contribution to journalArticle

Qin, Yong Jie ; Chan, Sun On ; Chong, Kelvin Kam Lung ; Li, Benjamin Fuk Loi ; Ng, Tsz Kin ; Yip, Yolanda Wong Ying ; Chen, Haoyu ; Zhang, Mingzhi ; Block, Norman L ; Cheung, Herman S ; Schally, Andrew V ; Pang, Chi Pui. / Antagonist of GH-releasing hormone receptors alleviates experimental ocular inflammation. In: Proceedings of the National Academy of Sciences of the United States of America. 2014 ; Vol. 111, No. 51. pp. 18303-18308.
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