title: When Beauty Is Skin Deep: Regulation of the Wound Response by Caspase-8, RIPK3, and the Inflammasome.
abstract: Caspase-8 downregulation is observed in the epidermis of wounded skin, whereas permanent epidermal caspase-8 deletion causes chronic skin inflammation, suggesting that caspase-8 is a critical regulator of skin homeostasis and, possibly, the wound response. In this issue, Lee et al. document how epidermal caspase-8 deletion, or cutaneous wounding, results in increased NF-κB activation to drive keratinocyte caspase-1 expression and subsequent secretion of the pro-inflammatory cytokines, IL-1β and IL-1α. Consequently, loss of NF-κB activity, caspase-1, or the IL-1 receptor delays wound healing. Previous studies have documented how chronic skin inflammation in caspase-8-deficient mice is rescued by RIPK3 co-deletion. Therefore, targeting caspase-1, IL-1, or RIPK3 itself may benefit treatment of chronic inflammatory skin diseases, or where an inappropriate inflammatory response proves detrimental to wound healing, such as in type 2 diabetes.
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia; Department of Medical Biology, University of Melbourne, Parkville, Victoria, Australia. Electronic address: vince@wehi.edu.au.
authors.forename: James E
authors.initials: JE
authors.lastname: Vince
mesh_terms: D000818:Animals; D020170:Caspase 1 / Q000502:physiology*; D060833:Cellular Microenvironment / Q000502:physiology*; D003872:Dermatitis / Q000473:pathology* / Q000503:physiopathology*; D015603:Keratinocytes / Q000473:pathology*
chemical_list: D020170:Caspase 1