Depilatory creams are widely used to remove unwanted body hair, but people with sensitive skin are subject to depilatory-induced skin burn/inflammation. It remains unknown what makes their skin more sensitive than others. In this study, we show that epidermal fatty acid‒binding protein (E-FABP) expressed in the skin plays a critical role in promoting depilatory-induced acute skin inflammation in mouse models. Although a depilatory cream removed hair by breaking down keratin disulfide bonds, it activated cytosolic phospholipase A2, leading to activation of the arachidonic acid/E-FABP/peroxisome proliferator–activated receptor β signaling pathway in keratinocytes. Specifically, peroxisome proliferator–activated receptor β activation induced downstream targets (e.g., cyclooxygenase 2) and chemokine (e.g., CXCL1) production, which systemically mobilized neutrophils and recruited them to localize in the skin for acute inflammatory responses. Importantly, E-FABP deletion by CRISPR-Cas9 reduced cytosolic phospholipase A2/peroxisome proliferator–activated receptor β activation in keratinocytes, and genetic deletion of E-FABP protected mice from depilatory cream-induced neutrophil recruitment and skin inflammation. Our findings suggest E-FABP as a molecular sensor for sensitive skin by triggering depilatory-induced, lipid-mediated skin inflammatory responses.
Bibliographical noteFunding Information:
The authors thank Rebecca Morris for help with skin cell separation protocol. This study was supported by R01AI137324 (to BL) and National Institutes of Health R01CA180986 (to BL).
The authors thank Rebecca Morris for help with skin cell separation protocol. This study was supported by R01AI137324 (to BL) and National Institutes of Health R01CA180986 (to BL). Conceptualization: BL, DY; Funding Acquisition: BL; Investigation: DY, RJ, JH, SRB, YH, YY, AA; Supervision: BL; Writing - Original Draft Preparation: DY, BL; Writing - Review and Editing: BL, NKE, BH, YD, ERS, The opinions expressed in this paper are the authors? own and do not reflect the view of the National Institutes of Health, the Department of Health and Human Services, or the United States government.
© 2021 The Authors
PubMed: MeSH publication types
- Journal Article
- Research Support, N.I.H., Extramural