title: Loss of epidermal p38α signaling prevents UVR-induced inflammation via acute and chronic mechanisms.
abstract: UVB is a component of solar radiation primarily responsible for causing damage and cancer in irradiated skin, and disrupting immune homeostasis. The immediate harm and long-term health risks of excessive sunlight exposure are affecting the lives of nearly all people worldwide. Inflammation is a key mechanism underlying UVB's various detrimental effects. Here we show that activation of the protein kinase p38α is restricted to the epidermis in UVB-exposed skin, and that p38α ablation targeted to the epithelial compartment is sufficient to suppress UVB-induced inflammation. Mechanistically, loss of epithelial p38α signaling attenuates the expression of genes required to induce vascular leakage and edema, and also increases the steady-state abundance of epidermal γδ T cells, which are known to promote the repair of damaged epidermis. These effects of p38α deficiency delineate a molecular network operating at the organism-environment interface, and reveal conditions crucial to preventing the pathology resulting from sun-damaged skin.
authors.affiliation: Cutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts, USA.
authors.forename: Yasuyo
authors.initials: Y
authors.lastname: Sano
authors.affiliation: Cutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts, USA. Electronic address: jmpark@cbrc2.mgh.harvard.edu.
authors.forename: Jin Mo
authors.initials: JM
authors.lastname: Park
mesh_terms: D000818:Animals; D051546:Cyclooxygenase 2 / Q000502:physiology; D003872:Dermatitis / Q000209:etiology / Q000517:prevention & control*; D004817:Epidermis / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000502:physiology; D014466:Ultraviolet Rays / Q000009:adverse effects*; D048051:p38 Mitogen-Activated Protein Kinases / Q000502:physiology*
chemical_list: D016692:Receptors, Antigen, T-Cell, gamma-delta; D051546:Cyclooxygenase 2; D048051:p38 Mitogen-Activated Protein Kinases