期刊
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY
卷 299, 期 4, 页码 G821-G832出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpgi.00178.2010
关键词
pancreatic cancer; pancreatitis; fibrosis; signal transduction; inflammation
资金
- Japan Society for the Promotion of Science
- Pancreas Research Foundation of Japan
- Kanae Foundation for Life and Socio-Medical Science
- Uehara Memorial Foundation
- Ministry of Health, Labour, and Welfare of Japan
Activated pancreatic stellate cells (PSCs) play a pivotal role in pancreatic fibrosis in chronic pancreatitis and pancreatic cancer. Recent studies have suggested a role of IL-33, a newly identified IL-1 family member, in fibrosis. We here examined the expression of IL-33 and the IL-33-mediated regulation of cell functions in PSCs. PSCs were isolated from human and rat pancreas tissues. The expression of IL-33 was examined by Western blotting, PCR, ELISA, and immunostaining. The roles of IL-33 in the regulation of PSC functions were examined by using recombinant IL-33 and small interfering RNA. Activated PSCs expressed IL-33 in the nucleus, and the expression was increased by IL-1 beta, TNF-alpha, PDGF-BB, and IFN-gamma, but not TGF-beta 1. Nuclear IL-33 expression was also observed in the pancreatic acinar and ductal cells. IL-1 beta induced IL-33 expression mainly through the activation of NF-kappa B and ERK pathways and partially through that of p38 MAP kinase, whereas PDGF-BB induced IL-33 expression mainly through the activation of ERK pathway. PSCs expressed soluble ST2, ST2L, and IL-1RAcP, but the expression level of ST2L was relatively low. Recombinant IL-33 did not stimulate key cell functions of PSCs. Decreased IL-33 expression by small interfering RNA resulted in decreased proliferation in response to PDGF-BB. In conclusion, activated PSCs expressed IL-33 in the nucleus. IL-33 might regulate the PDGF-induced proliferation in PSCs.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据