Contribution of TLR signaling to the pathogenesis of colitisassociated cancer in inflammatory bowel disease

作     者：Ferenc Sipos István Fri Miklós Constantinovits Zsolt Tulassay Gyrgyi Mzes 

作者机构：2nd Department of Internal Medicine Semmelweis University 1088 Budapest Hungary Molecular Medicine Research Unit Hungarian Academy of Sciences 1088 Budapest Hungary 

出 版 物：《World Journal of Gastroenterology》 (世界胃肠病学杂志（英文版）)

年 卷 期：2014年第20卷第36期

页      面：12713-12721页

核心收录：

学科分类：1002[医学-临床医学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学] 

主　　题：Inflammation Tissue repair Immunoregulation Colitis-associated cancer Toll-like receptor Inflammatory bowel disease Carcinogenesis 

摘      要：In the intestine a balance between proinflammatory and repair signals of the immune system is essential for the maintenance of intestinal homeostasis. The innate immunity ensures a primary host response to microbial invasion, which induces an inflammatory process to localize the infection and prevent systemic dissemination of pathogens. The key elements of this process are the germline encoded pattern recognition receptors including Toll-like receptors (TLRs). If pathogens cannot be eliminated, they may elicit chronic inflammation, which may be partly mediated via TLRs. Additionally, chronic inflammation has long been suggested to trigger tissue tumorous transformation. Inflammation, the seventh hallmark of cancer, may affect all phases of tumor development, and evade the immune system. Inflammation acts as a cellular stressor and may trigger DNA damage or genetic instability. Furthermore, chronic inflammation can provoke genetic mutations and epigenetic mechanisms that promote malignant cell transformation. Colorectal cancers in inflammatory bowel disease patients are considered typical examples of inflammation-related cancers. Although data regarding the role of TLRs in the pathomechanism of cancer-associated colitis are rather conflicting, functionally these molecules can be classified as largely antitumorigenic and largely pro-tumorigenic with the caveat that the underlying signaling pathways are mainly context (i.e., organ-, tissue-, cell-) and ligand-dependent.