title: Antagonist of GH-releasing hormone receptors alleviates experimental ocular inflammation.
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 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-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.
authors.affiliation: Department of Ophthalmology & Visual Sciences and.
authors.forename: Yong Jie
authors.initials: YJ
authors.lastname: Qin
authors.affiliation: School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong;
authors.forename: Sun On
authors.initials: SO
authors.lastname: Chan
authors.affiliation: Department of Ophthalmology & Visual Sciences and Joint Shantou International Eye Center, Shantou University and The Chinese University of Hong Kong, 515041 Shantou, China;
authors.forename: Kelvin Kam Lung
authors.initials: KK
authors.lastname: Chong
authors.affiliation: Department of Ophthalmology & Visual Sciences and.
authors.forename: Benjamin Fuk Loi
authors.initials: BF
authors.lastname: Li
authors.affiliation: Department of Ophthalmology & Visual Sciences and Joint Shantou International Eye Center, Shantou University and The Chinese University of Hong Kong, 515041 Shantou, China;
authors.forename: Tsz Kin
authors.initials: TK
authors.lastname: Ng
authors.affiliation: Department of Ophthalmology & Visual Sciences and.
authors.forename: Yolanda Wong Ying
authors.initials: YW
authors.lastname: Yip
authors.affiliation: Joint Shantou International Eye Center, Shantou University and The Chinese University of Hong Kong, 515041 Shantou, China;
authors.forename: Haoyu
authors.initials: H
authors.lastname: Chen
authors.affiliation: Joint Shantou International Eye Center, Shantou University and The Chinese University of Hong Kong, 515041 Shantou, China;
authors.forename: Mingzhi
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Biomedical Engineering, University of Miami, Coral Gables, FL 33146; Endocrine, Polypeptide, and Cancer Institute, South Florida Veterans Affairs Foundation for Research and Education, and Department of Pathology and Divisions of Hematology and Oncology and Endocrinology, Department of Medicine, Miller School of Medicine, University of Miami, Miami, FL 33136.
authors.forename: Norman L
authors.initials: NL
authors.lastname: Block
authors.affiliation: Department of Biomedical Engineering, University of Miami, Coral Gables, FL 33146; Geriatric Research, Education and Clinical Center, Veterans Affairs Medical Center, Miami, FL 33125; and.
authors.forename: Herman S
authors.initials: HS
authors.lastname: Cheung
authors.affiliation: Endocrine, Polypeptide, and Cancer Institute, South Florida Veterans Affairs Foundation for Research and Education, and Department of Pathology and Divisions of Hematology and Oncology and Endocrinology, Department of Medicine, Miller School of Medicine, University of Miami, Miami, FL 33136 andrew.schally@va.gov cppang@cuhk.edu.hk.
authors.forename: Andrew V
authors.initials: AV
authors.lastname: Schally
authors.affiliation: Department of Ophthalmology & Visual Sciences and Joint Shantou International Eye Center, Shantou University and The Chinese University of Hong Kong, 515041 Shantou, China; andrew.schally@va.gov cppang@cuhk.edu.hk.
authors.forename: Chi Pui
authors.initials: CP
authors.lastname: Pang
mesh_terms: D000818:Animals; D004797:Enzyme-Linked Immunosorbent Assay; D013006:Growth Hormone / Q000097:blood; D013007:Growth Hormone-Releasing Hormone / Q000627:therapeutic use*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018013:Receptors, Neuropeptide / Q000037:antagonists & inhibitors*; D018017:Receptors, Pituitary Hormone-Regulating Hormone / Q000037:antagonists & inhibitors*; D017337:Sermorelin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D014605:Uveitis / Q000517:prevention & control*
chemical_list: C550121:GHRH(1-29)NH2, (PhAc-Ada)(0)-Tyr(1), Arg(2), Fpa(5,6), Ala(8), Har(9), Tyr(Me)(10), His(11), Orn(12,) Abu(15), His(20), Orn(21), Nle(27), Arg(28), Har(29)-; D018013:Receptors, Neuropeptide; D018017:Receptors, Pituitary Hormone-Regulating Hormone; D007334:Insulin-Like Growth Factor I; D017337:Sermorelin; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone; C048250:somatotropin releasing hormone receptor
keywords: GHRH analogs; GHRH–GH–IGF1 axis; experimental uveitis