title: The role of mitogen- and stress-activated protein kinase 1 and 2 in chronic skin inflammation in mice.
abstract: Mitogen- and stress-activated protein kinase 1 and 2 (MSK1/2) are two kinases phosphorylated by both ERK1/2 and p38 MAPK. Recently, MSK1 and 2 have been reported to act as negative regulators of acute inflammation. In this study, we investigated the role of MSK1/2 in chronic skin inflammation using an oxazolone-induced allergic contact dermatitis model in MSK1/2 knockout mice and wild-type mice. MSK1/2 knockout mice were demonstrated to have significantly increased inflammation compared with wild-type mice. This was measured by an increased ear thickness, elevated infiltration of neutrophils in the skin and increased inflammatory histological changes. Furthermore, we found significantly elevated levels of the proinflammatory cytokines Tumor necrosis factor-α (TNF-α), IL-1β and IL-6 at both mRNA and protein levels in MSK1/2 knockout mice compared with wild-type mice after oxazolone treatment. In addition, the mRNA expression of the chemokine Thymus and activation regulated chemokine (TARC) was demonstrated to be significantly elevated in oxazolone-treated MSK1/2 knockout mice compared with wild-type mice. The increased expression of TARC was paralleled by increased infiltration of cells positive for the TARC receptor, CCR4, in the dermis of MSK1/2 knockout mice. Our results indicate that MSK1/2 are involved in the activation of feedback mechanisms that dampen oxazolone-induced skin inflammation.
authors.affiliation: Department of Dermatology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Trine
authors.initials: T
authors.lastname: Bertelsen
authors.forename: Lars
authors.initials: L
authors.lastname: Iversen
authors.forename: Jette Lindorff
authors.initials: JL
authors.lastname: Riis
authors.forename: J Simon C
authors.initials: JS
authors.lastname: Arthur
authors.forename: Bo Martin
authors.initials: BM
authors.lastname: Bibby
authors.forename: Knud
authors.initials: K
authors.lastname: Kragballe
authors.forename: Claus
authors.initials: C
authors.lastname: Johansen
mesh_terms: D000818:Animals; D054414:Chemokine CCL17 / Q000378:metabolism; D054425:Chemokine CCL27 / Q000378:metabolism; D017449:Dermatitis, Allergic Contact / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D004195:Disease Models, Animal; D005260:Female; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010081:Oxazolone / Q000009:adverse effects*; D038744:Ribosomal Protein S6 Kinases, 90-kDa / Q000235:genetics / Q000502:physiology*; D012867:Skin / Q000378:metabolism / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: C499538:Ccl17 protein, mouse; C119538:Ccl27a protein, mouse; D054414:Chemokine CCL17; D054425:Chemokine CCL27; D053583:Interleukin-1beta; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D010081:Oxazolone; D038744:Ribosomal Protein S6 Kinases, 90-kDa; C485459:Rps6ka4 protein, mouse; C116919:mitogen and stress-activated protein kinase 1