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Title: Role of hair follicles in the pathogenesis of arsenical-induced cutaneous damage.

Authors: Srivastava, Ritesh K; Wang, Yong; Khan, Jasim; Muzaffar, Suhail; Lee, Madison B; Weng, Zhiping; Croutch, Claire; Agarwal, Anupam; Deshane, Jessy; Athar, Mohammad

Published In Ann N Y Acad Sci, (2022 Sep)

Abstract: Arsenical vesicants cause skin inflammation, blistering, and pain. The lack of appropriate animal models causes difficulty in defining their molecular pathogenesis. Here, Ptch1+/- /C57BL/6 mice were employed to investigate the pathobiology of the arsenicals lewisite and phenylarsine oxide (PAO). Following lewisite or PAO challenge (24 h), the skin of animals becomes grayish-white, thick, leathery, and wrinkled with increased bi-fold thickness, Draize score, and necrotic patches. In histopathology, infiltrating leukocytes (macrophages and neutrophils), epidermal-dermal separation, edema, apoptotic cells, and disruption of tight and adherens junction proteins can be visualized. PCR arrays and nanoString analyses showed significant increases in cytokines/chemokines and other proinflammatory mediators. As hair follicles (HFs), which provide an immune-privileged environment, may affect immune cell trafficking and consequent inflammatory responses, we compared the pathogenesis of these chemicals in this model to that in Ptch1+/- /SKH-1 hairless mice. Ptch1+/- /SKH-1 mice have rudimentary, whereas Ptch1+/- /C57BL/6 mice have well-developed HFs. Although no significant differences were observed in qualitative inflammatory responses between the two strains, levels of cytokines/chemokines differed. Importantly, the mechanism of inflammation was identical; both reactive oxygen species induction and consequent activation of unfolded protein response signaling were similar. These data reveal that the acute molecular pathogenesis of arsenicals in these two murine models is similar.

PubMed ID: 35678766 Exiting the NIEHS site

MeSH Terms: Animals; Arsenicals*; Chemical Warfare Agents*/metabolism; Chemokines; Cytokines/metabolism; Hair Follicle/metabolism; Hair Follicle/pathology; Inflammation/pathology; Irritants; Mice; Mice, Hairless; Mice, Inbred C57BL; Reactive Oxygen Species/metabolism; Skin/metabolism

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Last Reviewed: December 05, 2024