title: TLR4/PKC-mediated tight junction modulation: a clinical marker of chemotherapy-induced gut toxicity?
abstract: Chemotherapy-induced gut toxicity is a major clinical and economic burden to oncology practice. The mechanisms responsible for its development are ill defined, hampering the development of therapeutic interventions. In light of newly published research foci and clinical practice guidelines in supportive care in cancer, there has been renewed interest in the role tight junctions play in the pathobiology of chemotherapy-induced gut toxicity. Several preclinical studies have identified molecular defects in intestinal tight junctions following chemotherapy. Despite these findings, the mechanisms responsible for chemotherapy-induced tight junction disruption remain unclear. Recent research has highlighted roles for toll-like receptor 4 and protein kinase C signalling in the regulation of tight junctions. This critical review therefore aims to provide evidence linking toll-like receptor 4 expression, protein kinase C activation and tight junction disruption and their relationship to clinical toxicity.
authors: Discipline of Anatomy and Pathology, School of Medical Sciences, University of Adelaide, Adelaide, Australia.
authors: Hannah R
authors: HR
authors: Wardill
authors: Rachel J
authors: RJ
authors: Gibson
authors: Richard M
authors: RM
authors: Logan
authors: Joanne M
authors: JM
authors: Bowen
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects*; D015415:Biomarkers / Q000378:metabolism*; D005767:Gastrointestinal Diseases / Q000139:chemically induced* / Q000378:metabolism; D006801:Humans; D011493:Protein Kinase C / Q000378:metabolism*; D015398:Signal Transduction; D019108:Tight Junctions / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D015415:Biomarkers; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D011493:Protein Kinase C
keywords: chemotherapy; mucositis; protein kinase C; tight junctions; toll-like receptor 4