Evidence for the involvement of keratinocyte-derived microvesicle particles in the photosensitivity associated with xeroderma pigmentosum type A deficiency.

Autor: Christian L; Department of Pharmacology & Toxicology, Wright State University, Dayton, Ohio, USA., Manjrekar P; Department of Pharmacology & Toxicology, Wright State University, Dayton, Ohio, USA., Henkels KM; Department of Pharmacology & Toxicology, Wright State University, Dayton, Ohio, USA., Rapp CM; Department of Pharmacology & Toxicology, Wright State University, Dayton, Ohio, USA., Annamraju R; Department of Pharmacology & Toxicology, Wright State University, Dayton, Ohio, USA., Lohade RP; Department of Pharmacology & Toxicology, Wright State University, Dayton, Ohio, USA., Singh S; Department of Pharmacology & Toxicology, Wright State University, Dayton, Ohio, USA., Carpenter MA; Department of Pharmacology & Toxicology, Wright State University, Dayton, Ohio, USA., Khan S; Department of Pharmacology & Toxicology, Wright State University, Dayton, Ohio, USA., Kemp MG; Department of Pharmacology & Toxicology, Wright State University, Dayton, Ohio, USA.; The Dayton V.A. Medical Center, Dayton, Ohio, USA., Chen Y; Department of Pharmacology & Toxicology, Wright State University, Dayton, Ohio, USA., Sahu RP; Department of Pharmacology & Toxicology, Wright State University, Dayton, Ohio, USA., Travers JB; Department of Pharmacology & Toxicology, Wright State University, Dayton, Ohio, USA.; The Dayton V.A. Medical Center, Dayton, Ohio, USA.; Department of Dermatology, Wright State University, Dayton, Ohio, USA.
Jazyk: angličtina
Zdroj: Photochemistry and photobiology [Photochem Photobiol] 2024 Sep-Oct; Vol. 100 (5), pp. 1457-1466. Date of Electronic Publication: 2024 Jan 29.
DOI: 10.1111/php.13915
Abstrakt: Photosensitivity can be due to numerous causes. The photosensitivity associated with deficiency of xeroderma pigmentosum type A (XPA) has been previously shown to be associated with excess levels of the lipid mediator platelet-activating factor (PAF) generated by the keratinocyte. As PAF has been reported to trigger the production of subcellular microvesicle particles (MVP) due to the enzyme acid sphingomyelinase (aSMase), the goal of these studies was to discern if PAF and aSMase could serve as therapeutic targets for the XPA deficiency photosensitivity. HaCaT keratinocytes lacking XPA generated greater levels of MVP in comparison to control cells. Mice deficient in XPA also generated enhanced MVP levels in skin and in plasma in response to UV radiation. Use of a genetic strategy with mice deficient in both XPA and PAF receptors revealed that these mice generated less MVP release as well as decreased skin erythema and cytokine release compared to XPA knockout mice alone. Finally, the aSMase inhibitor imipramine blocked UV-induced MVP release in HaCaT keratinocytes, as well as XPA knockout mice. These studies support the concept that the photosensitivity associated with XPA involves PAF- and aSMase-mediated MVP release and provides a potential pharmacologic target in treating this form of photosensitivity.
(© 2024 The Authors. Photochemistry and Photobiology published by Wiley Periodicals LLC on behalf of American Society for Photobiology.)
Databáze: MEDLINE
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