Role of tumor necrosis factor receptor 2 (TNFR2) in colonic epithelial hyperplasia and chronic intestinal inflammation in mice

Emiko Mizoguchi, Atsushi Mizoguchi, Hidetoshi Takedatsu, Elke Cario, Ype P. De Jong, Choon Jin Ooi, Ramnik J. Xavier, Cox Terhorst, Daniel K. Podolsky, Atul K. Bhan

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Abstract

Background & Aims: Tumor necrosis factor (TNF) induces multiple effects including cell proliferation and death by ligation with TNF receptor type II (TNFR2). We studied the role of TNFR2 in chronic inflammation-induced colonic epithelial alteration. Methods: TNFR2 expression in colonic epithelial cells (CECs) was assessed by ribonuclease protection assay (RPA) and immunohistochemistry (IHC) in patients with inflammatory bowel disease (IBD) and murine colitis models. TNFR2 expression was also analyzed using COLO205 cells. The role of TNFR2 in colonic epithelial homeostasis was examined by generating interleukin 6-deficient TCRαKO (αIL-6DKO) or TNFR2-deficient TCRα (αTNFR2DKO) mice. Results: TNFR2 expression was up-regulated in CEC in both human ulcerative colitis and Crohn's disease. In vitro studies showed that TNFR2 expression was upregulated by a cooperative effect of key proinflammatory cytokines. By RPA, the increased expression of TNFR2 was detectable in TCRαKO mice with colitis compared with TCRαKO mice without colitis or wild-type mice. In αIL-6DKO mice, TNFR2 expression, proliferation, and nuclear factor kappa B activation of CECs were markedly reduced compared with TCRαKO mice. αTNFR2 mice also showed significantly less colonic epithelial proliferation compared with TCRαKO mice. Conclusions: Expression of TNFR2 is consistently increased on CECs in both murine colitis models as well as patients with IBD. TNFR2 may play an important role in colonic inflammation-associated alteration in the intestinal epithelium.

Original languageEnglish (US)
Pages (from-to)134-144
Number of pages11
JournalGastroenterology
Volume122
Issue number1
StatePublished - 2002

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Receptors, Tumor Necrosis Factor, Type II
Hyperplasia
Inflammation
Colitis
Epithelial Cells
Ribonucleases
Inflammatory Bowel Diseases
Interleukin-6
NF-kappa B
Intestinal Mucosa
Ulcerative Colitis

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Mizoguchi, E., Mizoguchi, A., Takedatsu, H., Cario, E., De Jong, Y. P., Ooi, C. J., ... Bhan, A. K. (2002). Role of tumor necrosis factor receptor 2 (TNFR2) in colonic epithelial hyperplasia and chronic intestinal inflammation in mice. Gastroenterology, 122(1), 134-144.

Role of tumor necrosis factor receptor 2 (TNFR2) in colonic epithelial hyperplasia and chronic intestinal inflammation in mice. / Mizoguchi, Emiko; Mizoguchi, Atsushi; Takedatsu, Hidetoshi; Cario, Elke; De Jong, Ype P.; Ooi, Choon Jin; Xavier, Ramnik J.; Terhorst, Cox; Podolsky, Daniel K.; Bhan, Atul K.

In: Gastroenterology, Vol. 122, No. 1, 2002, p. 134-144.

Research output: Contribution to journalArticle

Mizoguchi, E, Mizoguchi, A, Takedatsu, H, Cario, E, De Jong, YP, Ooi, CJ, Xavier, RJ, Terhorst, C, Podolsky, DK & Bhan, AK 2002, 'Role of tumor necrosis factor receptor 2 (TNFR2) in colonic epithelial hyperplasia and chronic intestinal inflammation in mice', Gastroenterology, vol. 122, no. 1, pp. 134-144.
Mizoguchi E, Mizoguchi A, Takedatsu H, Cario E, De Jong YP, Ooi CJ et al. Role of tumor necrosis factor receptor 2 (TNFR2) in colonic epithelial hyperplasia and chronic intestinal inflammation in mice. Gastroenterology. 2002;122(1):134-144.
Mizoguchi, Emiko ; Mizoguchi, Atsushi ; Takedatsu, Hidetoshi ; Cario, Elke ; De Jong, Ype P. ; Ooi, Choon Jin ; Xavier, Ramnik J. ; Terhorst, Cox ; Podolsky, Daniel K. ; Bhan, Atul K. / Role of tumor necrosis factor receptor 2 (TNFR2) in colonic epithelial hyperplasia and chronic intestinal inflammation in mice. In: Gastroenterology. 2002 ; Vol. 122, No. 1. pp. 134-144.
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AU - De Jong, Ype P.

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AU - Xavier, Ramnik J.

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