title: Growth hormone secretagogue receptor is important in the development of experimental colitis.
abstract: BACKGROUND
  Growth hormone secretagogue receptor (GHSR) and its ligand, ghrelin, are important modulators in weight control and energy homeostasis. Recently, ghrelin is also involved in experimental colitis, but the role of GHSR in the development of colitis is unclear. The aim was to examine the underlying mechanism of GHSR in IBD development.
  
  
  METHODS
  The temporal expression of GHSR/ghrelin was determined in dextran sulphate sodium (DSS) induced colitis in Wt mice. The severity of DSS induced colitis from GHSR(-/-) and WT mice was compared at clinical/pathological levels. Furthermore, the function of macrophages was evaluated in vivo and in vitro.
  
  
  RESULTS
  Lack of GHSR attenuated colitis significantly at the clinical and pathological levels with reduced colonic pro-inflammatory cytokines (P < 0.05). This is consistent with the observation of less colonic macrophage infiltration and TLRs expression from DSS-treated GHSR(-/-) mice compared to WT mice (P < 0.05). Furthermore, there was significantly reduced pro-inflammatory cytokines in LPS-stimulated macrophages in vitro from GHSR(-/-) mice than WT mice (P < 0.05). Moreover, D-lys(3)-GHRP6 (a GHSR antagonist) reduced LPS-induced macrophage pro-inflammatory cytokines from WT mice in vitro.
  
  
  CONCLUSIONS
  GHSR contributes to development of acute DSS-induced colitis, likely via elevated pro-inflammatory cytokines and activation of macrophages. These data suggest GHSR as a potential therapeutic target for IBD.
authors.affiliation: School of Life Science and Technology, Tongji University, Shanghai, 200092 China.
authors.forename: Zhen-Ze
authors.initials: ZZ
authors.lastname: Liu
authors.affiliation: Shanghai Research Centre for Model Organisms, Shanghai, 201203 China.
authors.forename: Wei-Gang
authors.initials: WG
authors.lastname: Wang
authors.affiliation: School of Life Science and Technology, Tongji University, Shanghai, 200092 China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Li
authors.affiliation: School of Life Science and Technology, Tongji University, Shanghai, 200092 China.
authors.forename: Miao
authors.initials: M
authors.lastname: Tang
authors.affiliation: Shanghai Research Centre for Model Organisms, Shanghai, 201203 China.
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.affiliation: Shanghai Research Centre for Model Organisms, Shanghai, 201203 China.
authors.forename: Wen-Ting
authors.initials: WT
authors.lastname: Wu
authors.affiliation: Shanghai Research Centre for Model Organisms, Shanghai, 201203 China.
authors.forename: Ying-Han
authors.initials: YH
authors.lastname: Wan
authors.affiliation: Shanghai Research Centre for Model Organisms, Shanghai, 201203 China.
authors.forename: Zhu-Gang
authors.initials: ZG
authors.lastname: Wang
authors.affiliation: Discipline of Pathology, Bosch Institute and School of Medical Sciences, University of Sydney, Sydney, NSW 2006 Australia.
authors.forename: Shi-San
authors.initials: SS
authors.lastname: Bao
authors.affiliation: School of Life Science and Technology, Tongji University, Shanghai, 200092 China ; Shanghai Research Centre for Model Organisms, Shanghai, 201203 China.
authors.forename: Jian
authors.initials: J
authors.lastname: Fei
keywords: Colitis; D-lys3-GHRP6; Ghrelin; Growth hormone secretagogue receptor (GHSR); Macrophages
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