title: IL-1alpha accelerates stratum corneum formation and improves permeability barrier homeostasis during murine fetal development.
abstract: BACKGROUND
  The ontogenesis of the epidermal permeability barrier is complex and incompletely understood. Previously we showed that IL-1 and TNFalpha regulate permeability barrier homeostasis in adult mice.
  
  
  OBJECTIVE
  We determined whether IL-1 and TNFalpha also regulate fetal barrier development.
  
  
  METHODS
  Messenger RNA and protein levels in epidermis were determined by real-time PCR and immunohistochemistry, respectively. Epidermal ultra-structure was examined by electron microscopy.
  
  
  RESULTS
  The protein expression of IL-1alpha/beta and TNFalpha peaked in fetal rat epidermis at gestational age d19-20, a time point that coincides with the formation of a competent barrier. Treatment of fetal rat explants with IL-1 or TNFalpha accelerates barrier formation in a time- and dose-related fashion, evidenced by a decrease in transepidermal water loss attributable to the presence of mature morphology and an increase in the expression of cornified envelope proteins. Using single receptor KO mice, we demonstrated a delay in both barrier formation and cornified envelope protein expression, paralleled with immature lamellar membranes in epidermis of IL-1R KO, but not TNFR KO vs. wild-type at day 17, differences that disappeared in later gestational stages and immediately after birth. Using TNF receptor and IL-1 receptor double knock out (D-KO) mice, we further demonstrated that a transient delay in barrier development consistently occurs in epidermis of D-KO mice.
  
  
  CONCLUSIONS
  IL-1 plays a role in regulating the late stages of SC formation and permeability barrier ontogenesis.
authors.affiliation: Metabolism Section, Veterans Affairs Medical Center, and Departments of Dermatology and Medicine, University of California at San Francisco, United States. yan.jiang@med.va.gov <yan.jiang@med.va.gov>
authors.forename: Yan J
authors.initials: YJ
authors.lastname: Jiang
authors.forename: Biao
authors.initials: B
authors.lastname: Lu
authors.forename: Debra
authors.initials: D
authors.lastname: Crumrine
authors.forename: Mao-Qing
authors.initials: MQ
authors.lastname: Man
authors.forename: Peter M
authors.initials: PM
authors.lastname: Elias
authors.forename: Kenneth R
authors.initials: KR
authors.lastname: Feingold
mesh_terms: D000818:Animals; D004817:Epidermis / Q000196:embryology* / Q000378:metabolism / Q000648:ultrastructure; D006706:Homeostasis / Q000187:drug effects / Q000502:physiology; D053582:Interleukin-1alpha / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D053583:Interleukin-1beta / Q000378:metabolism / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D046529:Microscopy, Electron, Transmission; D009924:Organ Culture Techniques; D010539:Permeability / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D017472:Receptors, Interleukin-1 / Q000235:genetics / Q000378:metabolism*; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D053582:Interleukin-1alpha; D053583:Interleukin-1beta; D017472:Receptors, Interleukin-1; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha