期刊
JOURNAL OF PATHOLOGY
卷 225, 期 2, 页码 255-264出版社
WILEY-BLACKWELL
DOI: 10.1002/path.2933
关键词
gastritis; gastric cancer; gp130; IL-6; IL-17A; STAT3
资金
- Monash University Faculty (Medicine, Nursing and Health Sciences)
- Arthritis Research UK
- Microbiology Department
- Faculty of Medicine, Monash University
- National Health and Medical Research Council of Australia (NHMRC)
- Sylvia and Charles Viertel Charitable Foundation
- Monash University
- NHMRC
- Association for International Cancer Research
- Cancer Council of Victoria
- Versus Arthritis [18286] Funding Source: researchfish
Chronic activation of the gastric mucosal adaptive immune response is a characteristic trait of gastric cancer. It has recently emerged that a new class of T helper (Th) cells, defined by their ability to produce interleukin (IL)-17A (Th17), is associated with a host of inflammatory responses, including gastritis. However, the role of these Th17 cells in the pathogenesis of gastric cancer is less clear. To formally address this, we employed gp130(F/F) mice, which spontaneously develop gastric inflammation-associated tumours akin to human intestinal-type gastric cancer. At the molecular level, these tumours demonstrate hyper-activation of the latent transcription factor signal transducer and activator of transcription (STAT)3 via the IL-6 cytokine family member, IL-11. In gp130F/F mice, the generation of Th17 cells, as well as the gastric expression of IL-17a and other Th17-related factors (Ror gamma t, IL-23), were augmented compared to wild-type gp130(+/+) mice. Consistent with a role for IL-6 and STAT3 in regulating IL-17A, increased Th17 generation and gastric expression of Th17-related factors in gp130F/F mice were reduced to wild-type levels in gp130(F/F):Stat3(-/+) mice displaying normalized STAT3 activity, and also in gp130(F/F):IL-6(-/-) mice. Importantly, genetic ablation of IL-17A in gp130(F/F):IL-17a(-/-) mice did not suppress the initiation and growth of gastric tumours. Furthermore, IL-17A and RORC gene expression was strongly increased in human gastric biopsies from patients with gastritis, but not gastric cancer. Collectively, our data suggest that increased expression of Th17-related factors does not correlate with the molecular pathogenesis of gastric tumourigenesis.(#) Copyright (C) 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
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