Bacteroides fragilis Toxin Induces Sequential Proteolysis of E-Cadherin and Inflammatory Response in Mouse Intestinal Epithelial Cell Line

被引:0
作者
Kim, Woo-Seung [1 ]
Hwang, Soonjae [2 ]
Gwon, Sun-Yeong [3 ]
Jo, Minjeong [4 ]
Yoo, Sang-Hyeon [1 ]
Hong, Jiyun [1 ]
Jang, Ha-Neul [1 ]
Hong, Ju-Eun [1 ]
Kang, Da-Hye [5 ]
Yun, Miyong [6 ]
Rhee, Ki-Jong [1 ]
机构
[1] Yonsei Univ, Coll Software & Digital Healthcare Convergence, Dept Biomed Lab Sci, MIRAE Campus, Wonju 26493, South Korea
[2] Gachon Univ, Lee Gil Ya Canc & Diabet Inst, Coll Med, Dept Biochem, 155 Gaetbeol Ro, Inchon 21999, South Korea
[3] Korea Brain Res Inst, Neural Circuits Res Grp, Daegu 41062, South Korea
[4] St Jude Childrens Res Hosp, Dept Struct Biol, Memphis, TN 38105 USA
[5] Univ Missouri, Dept Obstet Gynecol & Womens Hlth, Columbia, MO 65211 USA
[6] Sejong Univ, Dept Bioind & Bioresource Engn, Coll Life Sci, Seoul 05006, South Korea
基金
新加坡国家研究基金会;
关键词
Bacteroides fragilis toxin; mouse epithelial cell; E-cadherin; KC; LIX; sTNFR1; PATHOGENICITY ISLAND; EXPRESSION; INTERLEUKIN-8; LOCALIZATION; ACTIVATION; COMMENSAL; PROTEIN; APC;
D O I
10.3390/microorganisms13040781
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Enterotoxigenic Bacteroides fragilis (ETBF) is an intestinal bacterium that secretes the metalloprotease Bacteroides fragilis toxin (BFT), which induces E-cadherin cleavage and interleukin-8 secretion in human intestinal epithelial cell lines. ETBF-induced E-cadherin cleavage is proposed to be the underlying reason for the promotion of colitis in ETBF-infected mice. However, a BFT-responsive murine cell line has not yet been reported. In the current study, we report that the mouse colonic epithelial cell line CMT93 undergoes E-cadherin ectodomain cleavage, cell rounding, and proliferation in response to BFT treatment. The amino acid sequence of the putative cleavage site of E-cadherin is identical in both BFT-responsive (CMT93) and BFT-nonresponsive (MSIE, CT26, YAMC, and B16) cell lines, suggesting that the E-cadherin amino acid sequence is not responsible for this observation. After E-cadherin ectodomain cleavage, the membrane-bound intracellular E-cadherin domain underwent cleavage by gamma-secretase and was subsequently degraded by the proteasome. Moreover, BFT induced the secretion of two chemokines (LIX and KC) and the formation of soluble TNFR1 in the CMT93 cell line. The identification of a BFT-responsive murine cell line may be used to elucidate the mechanism of ETBF pathogenesis in ETBF murine infection models.
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页数:16
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