Abstract
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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cyclooxygenase 2
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Cytokines / antagonists & inhibitors
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Enzyme Inhibitors / pharmacology
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Female
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HSP27 Heat-Shock Proteins
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Heat-Shock Proteins / metabolism
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Imidazoles / pharmacology
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Inflammation Mediators / antagonists & inhibitors
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Intracellular Signaling Peptides and Proteins
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Mice
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Mice, Hairless
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Phosphorylation / drug effects
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Phosphorylation / radiation effects
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Photosensitivity Disorders / etiology*
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Photosensitivity Disorders / metabolism
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Photosensitivity Disorders / pathology
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Prostaglandin-Endoperoxide Synthases / metabolism
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Protein Serine-Threonine Kinases / antagonists & inhibitors
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Protein Serine-Threonine Kinases / genetics
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Protein Serine-Threonine Kinases / metabolism
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Pyridines / pharmacology
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Signal Transduction / radiation effects
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Skin / enzymology
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Skin / metabolism
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Skin / pathology
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Skin / radiation effects
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Threonine
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Ultraviolet Rays*
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p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors
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p38 Mitogen-Activated Protein Kinases / metabolism*
Substances
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Cytokines
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Enzyme Inhibitors
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HSP27 Heat-Shock Proteins
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Heat-Shock Proteins
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Hspb2 protein, mouse
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Imidazoles
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Inflammation Mediators
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Intracellular Signaling Peptides and Proteins
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Pyridines
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SB 242235
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Threonine
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Cyclooxygenase 2
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Prostaglandin-Endoperoxide Synthases
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MAP-kinase-activated kinase 2
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Protein Serine-Threonine Kinases
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p38 Mitogen-Activated Protein Kinases