Growth hormone secretagogue receptor is important in the development of experimental colitis
详细信息 查看全文
- 作者：Zhen-ze Liu ; Wei-gang Wang ; Qing Li ; Miao Tang ; Jun Li ; Wen-ting Wu…
- 关键词：Growth hormone secretagogue receptor (GHSR) ; Ghrelin ; Colitis ; Macrophages ; D ; lys3 ; GHRP6
- 刊名：Cell & Bioscience
- 出版年：2015
- 出版时间：December 2015
- 年：2015
- 卷：5
- 期：1
- 全文大小：1,820 KB
- 参考文献：1. Kojima, M, Hosoda, H, Date, Y, Nakazato, M, Matsuo, H, Kangawa, K (1999) Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature 402: pp. 656-60 CrossRef
2. Tschop, M, Smiley, DL, Heiman, ML (2000) Ghrelin induces adiposity in rodents. Nature 407: pp. 908-13 CrossRef
3. Baatar, D, Patel, K, Taub, DD (2011) The effects of ghrelin on inflammation and the immune system. Mol Cell Endocrinol 340: pp. 44-58 CrossRef
4. Dixit, VD, Taub, DD (2005) Ghrelin and immunity: a young player in an old field. Exp Gerontol 40: pp. 900-10 CrossRef
5. Dixit, VD, Schaffer, EM, Pyle, RS, Collins, GD, Sakthivel, SK, Palaniappan, R (2004) Ghrelin inhibits leptin- and activation-induced proinflammatory cytokine expression by human monocytes and T cells. J Clin Invest 114: pp. 57-66 CrossRef
6. Chorny, A, Anderson, P, Gonzalez-Rey, E, Delgado, M (2008) Ghrelin protects against experimental sepsis by inhibiting high-mobility group box 1 release and by killing bacteria. J Immunol 180: pp. 8369-77 CrossRef
7. Zhao, D, Zhan, Y, Zeng, H, Moyer, MP, Mantzoros, CS, Pothoulakis, C (2006) Ghrelin stimulates interleukin-8 gene expression through protein kinase C-mediated NF-kappaB pathway in human colonic epithelial cells. J Cell Biochem 97: pp. 1317-27 CrossRef
8. Hanauer, SB (2006) Inflammatory bowel disease: epidemiology, pathogenesis, and therapeutic opportunities. Inflamm Bowel Dis 12: pp. S3-9 CrossRef
9. Wirtz, S, Neufert, C, Weigmann, B, Neurath, MF (2007) Chemically induced mouse models of intestinal inflammation. Nat Protoc 2: pp. 541-6 CrossRef
10. Smet, B, Thijs, T, Moechars, D, Colsoul, B, Polders, L, Ver Donck, L (2009) Endogenous and exogenous ghrelin enhance the colonic and gastric manifestations of dextran sodium sulphate-induced colitis in mice. Neurogastroenterol Motil 21: pp. 59-70 CrossRef
11. Wirtz, S, Becker, C, Blumberg, R, Galle, PR, Neurath, MF (2002) Treatment of T cell-dependent experimental colitis in SCID mice by local administration of an adenovirus expressing IL-18 antisense mRNA. J Immunol 168: pp. 411-20 CrossRef
12. Waseem, T, Duxbury, M, Ito, H, Ashley, SW, Robinson, MK (2008) Exogenous ghrelin modulates release of pro-inflammatory and anti-inflammatory cytokines in LPS-stimulated macrophages through distinct signaling pathways. Surgery 143: pp. 334-42 CrossRef
13. Xu, Y, Hunt, NH, Bao, S (2008) The role of granulocyte macrophage-colony-stimulating factor in acute intestinal inflammation. Cell Res 18: pp. 1220-9 CrossRef
14. Xu, Y, Hunt, NH, Bao, S (2007) The correlation between proinflammatory cytokines, MAdCAM-1 and cellular infiltration in the inflamed colon from TNF-alpha gene knockout mice. Immunol Cell Biol 85: pp. 633-9 CrossRef
15. Hosomi, S, Oshitani, N, Kamata, N, Sogawa, M, Yamagami, H, Watanabe, K (2008) Phenotypical and functional study of ghrelin and its receptor in the pathogenesis of Crohn’s disease. Inflamm Bowel Dis 14: pp. 1205-13 CrossRef
16. Peracchi, M, Bardella, MT, Caprioli, F, Massironi, S, Conte, D, Valenti, L (2006) Circulating ghrelin levels in patients with inflammatory bowel disease. Gut 55: pp. 432-3
文摘
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??/sup> 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--.05). This is consistent with the observation of less colonic macrophage infiltration and TLRs expression from DSS-treated GHSR??/sup> mice compared to WT mice (P--.05). Furthermore, there was significantly reduced pro-inflammatory cytokines in LPS-stimulated macrophages in vitro from GHSR??/sup> mice than WT mice (P--.05). Moreover, D-lys3-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.