title: Role of p38 mitogen-activated protein kinase isoforms in murine skin inflammation induced by 12-O-tetradecanoylphorbol 13-acetate.
abstract: p38 mitogen-activated protein kinase plays a pivotal role in skin inflammation. The purpose of this study was to investigate the role of the various p38 isoforms. p38β/δ-knockout-C57BL/6 mice were generated, studied in a 12-O-tetradecanoylphorbol 13-acetate (TPA)-induced skin inflammation model and compared with wild-type mice. The inflammatory response was determined by ear thickness, myeloperoxidase activity and histology. mRNA and protein expression of interleukin (IL)-1β and IL-6 was determined by quantitative real-time reverse transcription PCR and enzyme-linked immunoassay. In both groups application of TPA resulted in a significant increase in inflammation, and pretreatment with the p38α/β inhibitor, SB202190 resulted in a significant inhibition. A significantly slower onset but prolonged duration of the response was seen in p38β/δ knockout mice. This was paralleled by a significant, but transient, lower IL-1β and IL-6 protein expression in p38β/δ knockout mice. Although the p38α isoform is important, our data also demonstrate an important role of the p38β and/or δ isoforms in the regulation of TPA-induced skin inflammation.
authors.affiliation: Department of Dermatology, Aarhus University Hospital, Denmark.
authors.forename: Louise L
authors.initials: LL
authors.lastname: Lilleholt
authors.forename: Claus
authors.initials: C
authors.lastname: Johansen
authors.forename: J Simon
authors.initials: JS
authors.lastname: Arthur
authors.forename: Anne
authors.initials: A
authors.lastname: Funding
authors.forename: Bo M
authors.initials: BM
authors.lastname: Bibby
authors.forename: Knud
authors.initials: K
authors.lastname: Kragballe
authors.forename: Lars
authors.initials: L
authors.lastname: Iversen
mesh_terms: D000818:Animals; D003872:Dermatitis / Q000201:enzymology* / Q000209:etiology / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D004195:Disease Models, Animal; D004789:Enzyme Activation; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005786:Gene Expression Regulation; D007093:Imidazoles / Q000494:pharmacology; D018836:Inflammation Mediators / Q000378:metabolism; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D007527:Isoenzymes; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D048290:Mitogen-Activated Protein Kinase 11 / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D048292:Mitogen-Activated Protein Kinase 13 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D048308:Mitogen-Activated Protein Kinase 14 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000187:drug effects / Q000201:enzymology* / Q000276:immunology / Q000473:pathology; D013755:Tetradecanoylphorbol Acetate; D013997:Time Factors
chemical_list: D007093:Imidazoles; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D015850:Interleukin-6; D007527:Isoenzymes; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D012333:RNA, Messenger; D048292:Mitogen-Activated Protein Kinase 13; D048290:Mitogen-Activated Protein Kinase 11; D048308:Mitogen-Activated Protein Kinase 14; D013755:Tetradecanoylphorbol Acetate; C090942:4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)imidazole