title: [The role of TLR4 receptor in development of inflammation and carcinogenesis in ulcerative colitis and pharmacotherapy of this disorder].
abstract: Ulcerative colitis (UC), a form of inflammatory bowel disease, is characterized by recurrent exacerbation and remission periods. Disturbances in the TLR4 receptor pathway are suggested to be one of the potential mechanisms responsible for its development. TLR4 belongs to the toll-like receptor family, which is a part of the innate immune system. It is expressed in many cells, including enterocytes, and recognizes lipopolysaccharide of Gram-negative bacteria. The activated receptor leads to the development of the inflammatory reaction involving macrophages stimulated by chemokine CCL2, cyclooxygenase 2 (COX-2), prostaglandin E2 (PGE2) and tumor necrosis factor alpha (TNFalpha). On the other hand, this reaction is inhibited by anti-inflammatory agents, such as prostaglandin 15d-PGJ2, and peroxisome proliferator activated receptor type gamma (PPARgamma). Inflammation is aimed at increasing cell proliferation and rapid mucosal healing. The increased expression of TLR4 and the development of the uncontrolled inflammatory response in UC (increased production of COX-2, PGE2, TNFalpha and CCL2) impairs regeneration of the mucosa, resulting in its damage, and may later lead to the development of colon cancer. The aim of this study is to discuss the role of TLR4 in UC, and to indicate the role of the TLR4 pathway in the mechanism of action of the currently used drugs.
authors.affiliation: Katedra Farmakologii, Slaski Uniwersytet Medyczny w Katowicach. dawid_szumilas@wp.eu
authors.forename: Dawid
authors.initials: D
authors.lastname: Szumilas
authors.forename: Robert
authors.initials: R
authors.lastname: Krysiak
authors.forename: Bogusław
authors.initials: B
authors.lastname: Okopień
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D018932:Chemokine CCL2 / Q000276:immunology; D003093:Colitis, Ulcerative / Q000188:drug therapy* / Q000276:immunology*; D003110:Colonic Neoplasms / Q000276:immunology*; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology*; D008264:Macrophages / Q000276:immunology; D011453:Prostaglandins / Q000096:biosynthesis; D051197:Toll-Like Receptor 4 / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D018932:Chemokine CCL2; D011453:Prostaglandins; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha