PMID- 21166721 OWN - NLM STAT- MEDLINE DCOM- 20110621 LR - 20211020 IS - 1600-0625 (Electronic) IS - 0906-6705 (Linking) VI - 20 IP - 2 DP - 2011 Feb TI - The role of mitogen- and stress-activated protein kinase 1 and 2 in chronic skin inflammation in mice. PG - 140-5 LID - 10.1111/j.1600-0625.2010.01153.x [doi] AB - 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-alpha (TNF-alpha), IL-1beta 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. CI - (c) 2011 John Wiley & Sons A/S. FAU - Bertelsen, Trine AU - Bertelsen T AD - Department of Dermatology, Aarhus University Hospital, Aarhus, Denmark. FAU - Iversen, Lars AU - Iversen L FAU - Riis, Jette Lindorff AU - Riis JL FAU - Arthur, J Simon C AU - Arthur JS FAU - Bibby, Bo Martin AU - Bibby BM FAU - Kragballe, Knud AU - Kragballe K FAU - Johansen, Claus AU - Johansen C LA - eng GR - MC_U127081014/MRC_/Medical Research Council/United Kingdom PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20101217 PL - Denmark TA - Exp Dermatol JT - Experimental dermatology JID - 9301549 RN - 0 (Ccl17 protein, mouse) RN - 0 (Ccl27a protein, mouse) RN - 0 (Chemokine CCL17) RN - 0 (Chemokine CCL27) RN - 0 (Interleukin-1beta) RN - 0 (Interleukin-6) RN - 0 (Tumor Necrosis Factor-alpha) RN - 15646-46-5 (Oxazolone) RN - EC 2.7.11.1 (Ribosomal Protein S6 Kinases, 90-kDa) RN - EC 2.7.11.1 (Rps6ka4 protein, mouse) RN - EC 2.7.11.1 (mitogen and stress-activated protein kinase 1) SB - IM MH - Animals MH - Chemokine CCL17/metabolism MH - Chemokine CCL27/metabolism MH - Dermatitis, Allergic Contact/metabolism/pathology/*physiopathology MH - Disease Models, Animal MH - Female MH - Interleukin-1beta/metabolism MH - Interleukin-6/metabolism MH - Mice MH - Mice, Inbred C57BL MH - Mice, Knockout MH - Oxazolone/*adverse effects MH - Ribosomal Protein S6 Kinases, 90-kDa/genetics/*physiology MH - Skin/metabolism/pathology MH - Tumor Necrosis Factor-alpha/metabolism EDAT- 2010/12/21 06:00 MHDA- 2011/06/22 06:00 CRDT- 2010/12/21 06:00 PHST- 2010/12/21 06:00 [entrez] PHST- 2010/12/21 06:00 [pubmed] PHST- 2011/06/22 06:00 [medline] AID - 10.1111/j.1600-0625.2010.01153.x [doi] PST - ppublish SO - Exp Dermatol. 2011 Feb;20(2):140-5. doi: 10.1111/j.1600-0625.2010.01153.x. Epub 2010 Dec 17.