title: Understanding the connection between platelet-activating factor, a UV-induced lipid mediator of inflammation, immune suppression and skin cancer.
abstract: Lipid mediators of inflammation play important roles in several diseases including skin cancer, the most prevalent type of cancer found in the industrialized world. Ultraviolet (UV) radiation is a complete carcinogen and is the primary cause of skin cancer. UV radiation is also a potent immunosuppressive agent, and UV-induced immunosuppression is a well-known risk factor for skin cancer induction. An essential mediator in this process is the glyercophosphocholine 1-alkyl-2-acetyl-sn-glycero-3-phosphocholine commonly referred to as platelet-activating factor (PAF). PAF is produced by keratinocytes in response to diverse stimuli and exerts its biological effects by binding to a single specific G-protein-coupled receptor (PAF-R) expressed on a variety of cells. This review will attempt to describe how this lipid mediator is involved in transmitting the immunosuppressive signal from the skin to the immune system, starting from its production by keratinocytes, to its role in activating mast cell migration in vivo, and to the mechanisms involved that ultimately lead to immune suppression. Recent findings related to its role in regulating DNA repair and activating epigenetic mechanisms, further pinpoint the importance of this bioactive lipid, which may serve as a critical molecular mediator that links the environment (UVB radiation) to the immune system and the epigenome.
authors.affiliation: Dipartimento di Scienze della Vita e dell'Ambiente, Universita' Politecnica delle Marche, Ancona, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Damiani
authors.affiliation: Department of Immunology and The Center for Cancer Immunology Research, The University of Texas Graduate School for Biomedical Sciences at Houston, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Ullrich
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000378:metabolism; D004260:DNA Repair; D006801:Humans; D007165:Immunosuppression Therapy; D007249:Inflammation; D008407:Mast Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D010972:Platelet Activating Factor / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D012867:Skin / Q000378:metabolism / Q000528:radiation effects; D012878:Skin Neoplasms / Q000209:etiology* / Q000276:immunology / Q000378:metabolism; D014466:Ultraviolet Rays
chemical_list: D010972:Platelet Activating Factor; D043562:Receptors, G-Protein-Coupled