title: Therapeutic targeting of toll-like receptors in gastrointestinal inflammation.
abstract: Toll-like receptors (TLRs) are sensors of microbial products that initiate host defense responses in multicellular organisms. They are mainly linked to innate immunity and bridging to adaptive immunity, signaling through different TLRs responsible for a wide range of biological responses. The intracellular signaling pathways through Toll/interleukin-1 receptor (IL-1R) domains result in recruitment of the cytoplasmic adaptor molecules, with subsequent activation of a signaling cascade leading to nuclear factor-kappa B (NF-kappaB). TLR-signaling induces host inflammatory response and the inflammation becomes more severe in the absence of several extra and intra cellular negative regulators of TLR-signaling. In the intestine, TLR-dependent activation of NF-kappaB plays a vital role in maintaining epithelial homeostasis as well as regulating infections and inflammation, while dysregulation of TLR-signaling is associated with the pathogenesis of inflammatory bowel diseases (IBD). Recent findings regarding innate immunity-mediated regulation of intestinal pathophysiology prove that development of new drugs targeting TLRs including antagonists of TLR-signaling and agonists of their negative regulators has a potential impact on therapeutic strategies for intestinal inflammatory diseases.
authors.affiliation: Department of Gastroenterology and Hepatology, Shimane University School of Medicine, Izumo, Shimane, Japan. si360405@med.shimane-u.ac.jp
authors.forename: Shunji
authors.initials: S
authors.lastname: Ishihara
authors.forename: Mohammad A K
authors.initials: MA
authors.lastname: Rumi
authors.forename: Cesar-F
authors.initials: CF
authors.lastname: Ortega-Cava
authors.forename: Hideaki
authors.initials: H
authors.lastname: Kazumori
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Kadowaki
authors.forename: Norihisa
authors.initials: N
authors.lastname: Ishimura
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Kinoshita
mesh_terms: D000818:Animals; D005767:Gastrointestinal Diseases / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007113:Immunity, Innate; D007249:Inflammation / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D015398:Signal Transduction; D051193:Toll-Like Receptors / Q000037:antagonists & inhibitors* / Q000276:immunology*
chemical_list: D051193:Toll-Like Receptors