#Xlstat wayne state university skin#
The skin serves as an essential physical and immunological barrier to external insults and the entry of exogenous substances and microorganisms 7. Though the anti-inflammatory roles of resolvins are well known 3, the role of Alox15 (15-LOX encoding gene) deficiency in resolvin biosynthesis and skin integrity have not been fully investigated. Dysregulation of skin immunity and chronic inflammation are central pathogenic mechanisms underlying skin disease, and use of resolvins has been proposed as a therapeutic strategy 6. 15-Lipoxygenase (15-LOX) is responsible for the generation of resolvin D (RvD) synthesis from docosahexaenoic acid 5. Resolvins have been identified as one of the classes belonging to SPMs and they can be generated from the metabolism of omega-3 essential fatty acids by lipoxygenase and other lipid modifying enzymes 4. Among lipid derived signaling molecules, specialized proresolving lipid mediators (SPM) have been identified as endogenous lipid species that can contribute to natural resolution circuits 3. Lipid-derived signaling molecules regulate various cellular processes including cell survival, apoptosis, and metabolism 1, 2. Collectively, these results indicate that Alox15-mediated production of resolvin D2 is required to maintain skin integrity by suppressing dermal inflammation. Treatment with resolvin D2 reduced skin inflammation in Alox15 KO mice. Lipidomic analysis revealed severe loss of resolvin D2 in the dorsal skin of Alox15 KO mice compared to wild type controls. Alox15 deficiency increased infiltration of proinflammatory macrophages and upregulated proinflammatory and necroptotic signaling in dermal adipose tissue in the dorsal skin. Alox15 KO resulted in loss of hair follicle stem cells and abnormal transition of dermal adipocytes into fibroblasts. We demonstrated that knockout (KO) of Alox15 led to hair loss and disrupted the structural integrity of the dorsal skin. Here, we investigated anti-inflammatory role of Alox15 in skin homeostasis. 15-lipoxygenase is involved in the generation of specialized pro-resolving lipid mediators that play essential roles in resolution and inflammatory responses.
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