UVB Generates Microvesicle Particles via Platelet-activating Factor-receptor Signaling: A Novel Pathway by which a Skin-specific Stimulus Exerts Systemic EffectsPharmacology and Toxicology Faculty Publications
AbstractThough Ultraviolet B radiation (290-320 nm; UVB) exerts profound systemic effects, it is absorbed only in the epidermis. One important question in photobiology is how UVB signals are emanated from the epidermis. Microvesicle particles (MVP) are small (200-1000nm diameter) membrane-bound vesicles released by numerous cell types and can be found in the circulation. MVP can contain both nuclear and cytoplasmic components and are thought to provide a mechanism by which cells transmit signals systemically. Though various stressors have been demonstrated to generate MVP, the ability of UVB to exert this effect has not been demonstrated. Previous studies from ours and other groups have established that through its ability to act as a pro-oxidative stressor, UVB generates oxidized glycerophosphocholine (Ox-GPC) lipids with Platelet-activating Factor-receptor (PAF-R) agonist activity. Our first studies examined the ability of UVB to stimulate the release of MVP. Treatment of the human keratinocyte-derived cell line HaCaT with UVB resulted in the release of MVP. Treatment of HaCaT cells with the PAF-R agonist carbamoyl-PAF (CPAF) also generated MVP release. Preincubation of HaCaT cells with antioxidants N-acetyl cysteine and vitamin C blocked MVP release in response to UVB, but had no effect on MVP release in response to CPAF. To confirm that UVB generates MVP via PAF-R agonists, we used a human epithelial cell line with/without PAF-Rs. UVB generated MVP only in the PAF-R-expressing (KBP) not the PAF-R-negative (KBM) cells. Finally, we induced suction blisters on human skin explants and human skin in vivo and tested the ability of UVB irradiation of these blisters to induce MVP release into blister fluid. These experiments determined that UVB generated MVP in human skin. These studies describe a new pathway involving MVP generated following UVB-induced PAF agonist formation that could play an important role in transmitting systemic signals following this environmental pro-oxidative stressor.
Citation InformationJeffrey B. Travers, Christine M. Rapp, Katherine E. Fahy, Christina E. Borchers, et al.. "UVB Generates Microvesicle Particles via Platelet-activating Factor-receptor Signaling: A Novel Pathway by which a Skin-specific Stimulus Exerts Systemic Effects" (2016)
Available at: http://works.bepress.com/christina_borchers/6/