title: From extracellular to intracellular targets, inhibiting MAP kinases in treatment of Crohn's disease.
abstract: In recent years the emphasis in finding new therapeutic options for chronic inflammatory diseases has been on targeting extracellular mediators of inflammation. A range of tools has become available to interfere with signaling by cytokines and their receptors. As our understanding of the intracellular pathways that mediate inflammatory signals expands, new therapeutic targets within the inflammatory cells come into sight. In this review we will discuss possible intracellular targets for treatment in Crohn's disease, a chronic relapsing inflammatory disease of the gut. Despite the encouraging results with anti-TNF antibodies in patients with Crohn's disease, our current treatment options are still insufficient and warrant novel treatment strategies. The mitogen-activated protein kinase (MAPK) family of signal transduction proteins is an important intracellular mediator of inflammation, and recently a MAPK inhibitor was successfully used in patients with Crohn's disease. We will discuss our current understanding of the molecular pathophysiology of Crohn's disease and also novel therapies that specifically target members of the MAPK pathway.
authors.affiliation: Laboratory for Experimental Internal Medicine Academic Medical Center, 1105 AZ Amsterdam, the Netherlands. B.vandenBlink@amc.uva.nl
authors.forename: Bernt
authors.initials: B
authors.lastname: Van Den Blink
authors.forename: Tessa
authors.initials: T
authors.lastname: Ten Hove
authors.forename: Gijs R
authors.initials: GR
authors.lastname: Van Den Brink
authors.forename: Maikel P
authors.initials: MP
authors.lastname: Peppelenbosch
authors.forename: Sander J H
authors.initials: SJ
authors.lastname: Van Deventer
mesh_terms: D003424:Crohn Disease / Q000188:drug therapy* / Q000201:enzymology*; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005110:Extracellular Space / Q000502:physiology; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000502:physiology; D020382:Interleukin-18 / Q000502:physiology; D007424:Intracellular Fluid / Q000502:physiology; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors*; D008954:Models, Biological; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
chemical_list: D004791:Enzyme Inhibitors; D020382:Interleukin-18; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12; D007371:Interferon-gamma; D020928:Mitogen-Activated Protein Kinases