Role of p38 MAPK in UVB-induced inflammatory responses in the skin of SKH-1 hairless mice

J Invest Dermatol. 2005 Jun;124(6):1318-25. doi: 10.1111/j.0022-202X.2005.23747.x.

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

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cyclooxygenase 2
  • Cytokines / antagonists & inhibitors
  • Enzyme Inhibitors / pharmacology
  • Female
  • HSP27 Heat-Shock Proteins
  • Heat-Shock Proteins / metabolism
  • Imidazoles / pharmacology
  • Inflammation Mediators / antagonists & inhibitors
  • Intracellular Signaling Peptides and Proteins
  • Mice
  • Mice, Hairless
  • Phosphorylation / drug effects
  • Phosphorylation / radiation effects
  • Photosensitivity Disorders / etiology*
  • Photosensitivity Disorders / metabolism
  • Photosensitivity Disorders / pathology
  • Prostaglandin-Endoperoxide Synthases / metabolism
  • Protein-Serine-Threonine Kinases / antagonists & inhibitors
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism
  • Pyridines / pharmacology
  • Signal Transduction / radiation effects
  • Skin / enzymology
  • Skin / metabolism
  • Skin / pathology
  • Skin / radiation effects
  • Threonine
  • Ultraviolet Rays*
  • p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • p38 Mitogen-Activated Protein Kinases / metabolism*

Substances

  • Cytokines
  • Enzyme Inhibitors
  • HSP27 Heat-Shock Proteins
  • Heat-Shock Proteins
  • Hspb2 protein, mouse
  • Imidazoles
  • Inflammation Mediators
  • Intracellular Signaling Peptides and Proteins
  • Pyridines
  • SB 242235
  • Threonine
  • Cyclooxygenase 2
  • Prostaglandin-Endoperoxide Synthases
  • MAP-kinase-activated kinase 2
  • Protein-Serine-Threonine Kinases
  • p38 Mitogen-Activated Protein Kinases