Glial-derived neurotrophic factor regulates enteric mast cells and ameliorates dextran sulfate sodium-induced experimental colitis期刊界 All Journals 搜尽天下杂志传播学术成果专业期刊搜索期刊信息化学术搜索

Glial-derived neurotrophic factor regulates enteric mast cells and ameliorates dextran sulfate sodium-induced experimental colitis

Affiliation:	1. Department of Geriatrics and National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China;2. Department of Gastroenterology and the Center of Inflammatory Bowel Disease, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China;3. Department of Geriatric Medicine and Gastroenterology, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu 611731, China;4. Chinese Academy of Sciences Sichuan Translational Medical Research Hospital, Chengdu 610072, China

Abstract:	Background & AimsAlthough interactions between enteric glial cells (EGCs) and enteric mast cells have been demonstrated to play an important role in the pathogenesis of inflammatory bowel disease (IBD), the exact mechanisms by which EGCs regulate enteric mast cells are still unknown. The aims of this study were to investigate whether glial-derived neurotrophic factor (GDNF), which has been confirmed to be produced mostly by EGCs, might regulate enteric mast cells and ameliorate dextran sulfate sodium (DSS)-induced experimental colitis.MethodsRecombinant adenoviral vectors encoding GDNF (Ad-GDNF) were administered intracolonically in experimental colitis induced by DSS. The disease activity index and histological score were measured. The expression of tumour necrosis factor-α (TNF-α), interleukin-6 and myeloperoxidase (MPO) activity were measured by ELISA assay. The expression of trypsin and β-hexosaminidase were evaluated. GDNF specific receptor (GFR-α1/RET) was detected. The calcium reflux was tested by microplate reader. The expression p-JNK was analyzed by western blot assay.ResultsGDNF resulted in a significant inhibition of the activation of enteric mast cells by down-regulating JNK signal pathway, lessening intracellular calcium influx, and then reducing the degranulation as well as the expression of pro-inflammatory cytokines via combing with its receptor (GFR-α1/RET) in mast cells, and these inhibitory effects were abrogated by treatment with neutralizing antibody against GDNF. Moreover, the administration of GDNF led to an amelioration of experimental colitis.ConclusionsGDNF are able to regulate enteric mast cells and ameliorate experimental colitis. GDNF might be an important mediator of the cross-talk between EGCs and enteric mast cells, and GDNF might be a useful therapeutic drug for IBD.

Keywords:	Enteric glial cell Glial-derived neurotrophic factor (GDNF) Mast cell Inflammatory bowel disease (IBD) EGCs"} {"#name":"keyword" "$":{"id":"k0030"} "$$":[{"#name":"text" "_":"enteric glial cells IBD"} {"#name":"keyword" "$":{"id":"k0040"} "$$":[{"#name":"text" "_":"inflammatory bowel disease GDNF"} {"#name":"keyword" "$":{"id":"k0050"} "$$":[{"#name":"text" "_":"glial-derived neurotrophic factor DSS"} {"#name":"keyword" "$":{"id":"k0060"} "$$":[{"#name":"text" "_":"dextran sulphate sodium TNF-α"} {"#name":"keyword" "$":{"id":"k0070"} "$$":[{"#name":"text" "_":"tumour necrosis factor-α IL-6"} {"#name":"keyword" "$":{"id":"k0080"} "$$":[{"#name":"text" "_":"interleukin-6 MPO"} {"#name":"keyword" "$":{"id":"k0090"} "$$":[{"#name":"text" "_":"myeloperoxidase GFR-α1 glial-derived neurotrophic factor receptor-α1 RET"} {"#name":"keyword" "$":{"id":"k0100"} "$$":[{"#name":"text" "_":"receptor tyrosine kinase JNK"} {"#name":"keyword" "$":{"id":"k0110"} "$$":[{"#name":"text" "_":"c-Jun N-terminal kinase ENS"} {"#name":"keyword" "$":{"id":"k0120"} "$$":[{"#name":"text" "_":"enteric nervous system DNP-IgE"} {"#name":"keyword" "$":{"id":"k0130"} "$$":[{"#name":"text" "_":"Dinitrophenylated immunoglobuli E DNP-HSA"} {"#name":"keyword" "$":{"id":"k0140"} "$$":[{"#name":"text" "_":"Dinitrophenylated human serum albumin Ad-GDNF"} {"#name":"keyword" "$":{"id":"k0150"} "$$":[{"#name":"text" "_":"recombinant adenoviral vectors encoding GDNF EGFP"} {"#name":"keyword" "$":{"id":"k0160"} "$$":[{"#name":"text" "_":"enhanced green fluorescent protein gene DAI"} {"#name":"keyword" "$":{"id":"k0170"} "$$":[{"#name":"text" "_":"disease activity index ELISA"} {"#name":"keyword" "$":{"id":"k0180"} "$$":[{"#name":"text" "_":"enzyme-linked immune-sorbent assay
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