研究人員發(fā)現(xiàn),，部分腸菌類細菌能引發(fā)結腸癌,，這一揭示出這種疾病的一種分子機理的新成果發(fā)表在8月在線出版的《自然—醫(yī)學》期刊上,。
Cynthia Sears和同事研究了這樣的問題：由產腸毒素脆弱類桿菌（ETBF）導致的腸道定殖如何引發(fā)了結腸癌。他們發(fā)現(xiàn),，產腸毒素脆弱類桿菌和無毒素脆弱類桿菌都會在小鼠腸道內定殖,，但只有產腸毒素脆弱類桿菌會誘發(fā)結腸炎癥和腫瘤。這些癥狀與白細胞介素17（IL—17）發(fā)出的細胞信號的增加有關,。關鍵是,，阻斷IL—17或IL—23調節(jié)的信號，可抑制產腸毒素脆弱類桿菌誘導的炎癥和腫瘤形成,。
新發(fā)現(xiàn)顯示,，一種依賴于IL—17的通道與炎癥引發(fā)型癌癥有關，而這種癌癥則是由一種普通的腸菌類所致,。這一新發(fā)現(xiàn)揭示出人類結腸類癌癥的一種分子機制,，從而打開了一扇治療這種疾病的大門。（生物谷Bioon.com）
生物谷推薦原始出處：
Nature Medicine 15, 1016 - 1022 (2009) 23 August 2009 | doi:10.1038/nm.2015
A human colonic commensal promotes colon tumorigenesis via activation of T helper type 17 T cell responses
Shaoguang Wu1,8, Ki-Jong Rhee1,7,8, Emilia Albesiano2, Shervin Rabizadeh3,8, Xinqun Wu1,2, Hung-Rong Yen2,4, David L Huso5, Frederick L Brancati1, Elizabeth Wick6, Florencia McAllister1,2, Franck Housseau2, Drew M Pardoll1,2 & Cynthia L Sears1,2
Abstract
The intestinal flora may promote colon tumor formation. Here we explore immunologic mechanisms of colonic carcinogenesis by a human colonic bacterium, enterotoxigenic Bacteroides fragilis (ETBF). ETBF that secretes B. fragilis toxin (BFT) causes human inflammatory diarrhea but also asymptomatically colonizes a proportion of the human population. Our results indicate that whereas both ETBF and nontoxigenic B. fragilis (NTBF) chronically colonize mice, only ETBF triggers colitis and strongly induces colonic tumors in multiple intestinal neoplasia (Min) mice. ETBF induces robust, selective colonic signal transducer and activator of transcription-3 (Stat3) activation with colitis characterized by a selective T helper type 17 (TH17) response distributed between CD4+ T cell receptor- (TCR)+ and CD4–8–TCR+ T cells. Antibody-mediated blockade of interleukin-17 (IL-17) as well as the receptor for IL-23, a key cytokine amplifying TH17 responses, inhibits ETBF-induced colitis, colonic hyperplasia and tumor formation. These results show a Stat3- and TH17-dependent pathway for inflammation-induced cancer by a common human commensal bacterium, providing new mechanistic insight into human colon carcinogenesis.
1 Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
2 Department of Oncology and the Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
3 Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
4 Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University and Center for Traditional Chinese Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
5 Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
6 Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
7 Present addresses: Department of Medicine, University of Illinois, Chicago, Illinois, USA (K.-J.R.) and Cedars Sinai Medical Center, Los Angeles, California, USA (S.R.).
8 These authors contributed equally to this work.
