title: Reduced oxazolone-induced skin inflammation in MAPKAP kinase 2 knockout mice.
abstract: Mitogen-activated protein kinase (MAPK) AP kinase 2 (MK2) is a serine/threonine kinase that is phosphorylated and activated by p38 MAPK. MK2 regulates the expression of various proinflammatory cytokines including TNF-alpha, IL-1beta, IL-6, and IL-8. Recently, MK2 was demonstrated to be activated in lesional psoriatic epidermis. This study investigates for the first time the role of MK2 in skin inflammation using the model of oxazolone-induced acute allergic contact dermatitis in mice. We show that oxazolone treatment leads to increased expression and sustained activation of both p38 MAPK and MK2. The inflammatory response was determined by ear thickness, myeloperoxidase activity, and histology after oxazolone challenge. Pretreatment with the p38 MAPK inhibitor SB202190 and genetic ablation of MK2 inhibit this inflammatory response. In particular, IL-1beta and, to a smaller but significant extent, also TNF-alpha and IFN-gamma expression were decreased in MK2 knockout mice compared with wild-type mice. These results indicate that MK2 is a potential target for the treatment of inflammatory skin diseases.
authors.affiliation: Department of Dermatology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Anne T
authors.initials: AT
authors.lastname: Funding
authors.forename: Claus
authors.initials: C
authors.lastname: Johansen
authors.forename: Matthias
authors.initials: M
authors.lastname: Gaestel
authors.forename: Bo M
authors.initials: BM
authors.lastname: Bibby
authors.forename: Louise L
authors.initials: LL
authors.lastname: Lilleholt
authors.forename: Knud
authors.initials: K
authors.lastname: Kragballe
authors.forename: Lars
authors.initials: L
authors.lastname: Iversen
mesh_terms: D000818:Animals; D017449:Dermatitis, Allergic Contact / Q000209:etiology*; D007093:Imidazoles / Q000494:pharmacology; D007371:Interferon-gamma / Q000235:genetics; D053583:Interleukin-1beta / Q000235:genetics; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010081:Oxazolone / Q000633:toxicity*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*; D011725:Pyridines / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology; D000099190:MAP-Kinase-Activated Kinase 2
chemical_list: D007093:Imidazoles; D007371:Interferon-gamma; D053583:Interleukin-1beta; D047908:Intracellular Signaling Peptides and Proteins; D010081:Oxazolone; D017346:Protein Serine-Threonine Kinases; D011725:Pyridines; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D048051:p38 Mitogen-Activated Protein Kinases; D000099190:MAP-Kinase-Activated Kinase 2; C090942:4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)imidazole