title: Involvement of JAK/STAT signaling in the pathogenesis of inflammatory bowel disease.
abstract: The Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway constitute the fulcrum in many vital cellular processes, including cell growth, differentiation, proliferation, and regulatory immune functions. Various cytokines, growth factors, and protein tyrosine kinases communicate through the JAK/STAT pathway and regulate the transcription of numerous genes. In addition to their critical roles in a plethora of key cellular activities, the JAK/STAT signaling pathways also have been implicated in the pathogenesis of several diseases, including inflammatory bowel disease (IBD), especially since a JAK inhibitor recently has been shown to be effective in the treatment of ulcerative colitis. The aim of this review is to highlight the recent findings on the regulatory mechanism of JAK/STAT signaling pathways and to reveal the evolving comprehension of their interface which might be of interest for clinicians involved in IBD therapy. Further, it is described how these signaling pathways have been exploited for the development of promising novel JAK inhibitors with anti-inflammatory effects verified in clinical trials.
authors.affiliation: Department of Gastroenterology, Medical Section, Herlev Hospital, University of Copenhagen, Denmark. Electronic address: mehmet.coskun@regionh.dk.
authors.forename: Mehmet
authors.initials: M
authors.lastname: Coskun
authors.forename: Mohammad
authors.initials: M
authors.lastname: Salem
authors.forename: Jannie
authors.initials: J
authors.lastname: Pedersen
authors.forename: Ole Haagen
authors.initials: OH
authors.lastname: Nielsen
mesh_terms: D000818:Animals; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D053612:Janus Kinases / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism*; D010880:Piperidines / Q000627:therapeutic use; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011743:Pyrimidines / Q000627:therapeutic use; D011758:Pyrroles / Q000627:therapeutic use; D050791:STAT Transcription Factors / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D010880:Piperidines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D011758:Pyrroles; D050791:STAT Transcription Factors; C479163:tofacitinib; D053612:Janus Kinases
keywords: CD; Crohn's disease; DSS; IBD; IEC; IFN; IL; Inflammatory bowel disease; JAK; Janus kinase; LDL; RA; ROR; STAT; T helper; TNF; TYK; Th; Tofacitinib; Treg; UC; Ulcerative colitis; dextran sodium sulfate; inflammatory bowel disease; interferon; interleukin; intestinal epithelial cell; low-density lipoprotein; regulatory T; retinoid-related orphan receptor; rheumatoid arthritis; signal transducer and activator of transcription; tumor necrosis factor; tyrosine kinase; ulcerative colitis