Epidermal Fatty Acid-Binding Protein Mediates Depilatory-Induced Acute Skin Inflammation

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 proliferatoreactivated receptor beta signaling pathway in keratinocytes. Specifically, peroxisome proliferatoreactivated receptor beta 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 proliferatoreactivated receptor beta 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.

Automated summary

Depilatory creams can cause skin inflammation in people with sensitive skin, but the reasons for their increased sensitivity are unknown. This study shows that epidermal fatty acid-binding protein (E-FABP) plays a critical role in promoting depilatory-induced acute skin inflammation in mouse models. The activation of multiple signaling pathways in keratinocytes by depilatory creams leads to the inflammatory response.