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.
MeSH terms
-
Animals
-
Dermatitis / enzymology*
-
Dermatitis / etiology
-
Dermatitis / immunology
-
Dermatitis / pathology
-
Dermatitis / prevention & control
-
Disease Models, Animal
-
Enzyme Activation
-
Enzyme-Linked Immunosorbent Assay
-
Female
-
Gene Expression Regulation
-
Imidazoles / pharmacology
-
Inflammation Mediators / metabolism
-
Interleukin-1beta / genetics
-
Interleukin-1beta / metabolism
-
Interleukin-6 / genetics
-
Interleukin-6 / metabolism
-
Isoenzymes
-
Mice
-
Mice, Inbred C57BL
-
Mice, Knockout
-
Mitogen-Activated Protein Kinase 11 / antagonists & inhibitors
-
Mitogen-Activated Protein Kinase 11 / deficiency
-
Mitogen-Activated Protein Kinase 11 / genetics
-
Mitogen-Activated Protein Kinase 11 / metabolism*
-
Mitogen-Activated Protein Kinase 13 / deficiency
-
Mitogen-Activated Protein Kinase 13 / genetics
-
Mitogen-Activated Protein Kinase 13 / metabolism*
-
Mitogen-Activated Protein Kinase 14 / antagonists & inhibitors
-
Mitogen-Activated Protein Kinase 14 / metabolism*
-
Protein Kinase Inhibitors / pharmacology
-
Pyridines / pharmacology
-
RNA, Messenger / metabolism
-
Reverse Transcriptase Polymerase Chain Reaction
-
Skin / drug effects
-
Skin / enzymology*
-
Skin / immunology
-
Skin / pathology
-
Tetradecanoylphorbol Acetate*
-
Time Factors
Substances
-
Imidazoles
-
Inflammation Mediators
-
Interleukin-1beta
-
Interleukin-6
-
Isoenzymes
-
Protein Kinase Inhibitors
-
Pyridines
-
RNA, Messenger
-
Mitogen-Activated Protein Kinase 13
-
Mitogen-Activated Protein Kinase 11
-
Mitogen-Activated Protein Kinase 14
-
Tetradecanoylphorbol Acetate
-
4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)imidazole