Role of p38 MAPK in UVB-induced inflammatory responses in the skin of SKH-1 hairless mice.
The p38 mitogen-activated protein kinase (MAPK) signaling pathway is activated by numerous inflammatory mediators and environmental stresses. We assessed the effects of ultraviolet B (UVB) on the p38 MAPK pathway and determined whether cyclooxygenase (COX)-2 expression is downstream of this kinase in the skin of UVB-irradiated SKH-1 mice. SKH-1 mice were irradiated with a single dose of UVB (360 mJ per cm2), and activation of the epidermal p38 MAPK pathway was assessed. UVB-induced phosphorylation of p38 MAPK occurred in a time-dependent manner. Phosphorylation of MAPK-activated protein kinase-2 (MAPKAPK-2) also was detected and correlated with an increase in its kinase activity. Phosphorylation of heat shock protein 27 (HSP27), a substrate for MAPKAPK-2, also was detected post-irradiation. Oral administration of the p38 inhibitor, SB242235, prior to UVB irradiation, blocked activation of the p38 MAPK cascade, and abolished MAPKAPK-2 kinase activity and phosphorylation of HSP27. Moreover, SB242235 inhibited expression of the pro-inflammatory cytokines interleukin (IL)-6 and KC (murine IL-8) and COX-2. Our data demonstrate that UVB irradiation of murine skin activates epidermal p38 MAPK signaling and induces a local pro-inflammatory response. Blockade of the p38 MAPK pathway may offer an effective approach to reducing or preventing skin damage resulting from acute solar radiation.
Kim
Arianna L
AL
Department of Dermatology, Columbia University College of Physicians & Surgeons, New York, New York 10032, USA. ak309@columbia.edu
Labasi
Jeffrey M
JM
Zhu
Yucui
Y
Tang
Xiuwei
X
McClure
Kim
K
Gabel
Christopher A
CA
Athar
Mohammad
M
Bickers
David R
DR
D000818:Animals; D051546:Cyclooxygenase 2; D016207:Cytokines / Q000037:antagonists & inhibitors; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D055551:HSP27 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000378:metabolism; D007093:Imidazoles / Q000494:pharmacology; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D008812:Mice, Hairless; D010766:Phosphorylation / Q000187:drug effects / Q000528:radiation effects; D010787:Photosensitivity Disorders / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D015398:Signal Transduction / Q000528:radiation effects; D012867:Skin / Q000201:enzymology / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects; D013912:Threonine; D014466:Ultraviolet Rays; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000099190:MAP-Kinase-Activated Kinase 2
D051546:Cyclooxygenase 2; D016207:Cytokines; D004791:Enzyme Inhibitors; D055551:HSP27 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D007093:Imidazoles; D018836:Inflammation Mediators; D047908:Intracellular Signaling Peptides and Proteins; D011451:Prostaglandin-Endoperoxide Synthases; D017346:Protein Serine-Threonine Kinases; D011725:Pyridines; D013912:Threonine; D048051:p38 Mitogen-Activated Protein Kinases; D000099190:MAP-Kinase-Activated Kinase 2; C486699:Hspb2 protein, mouse; C403289:SB 242235