title: IL-6 stimulates but is not essential for stratum corneum formation and permeability barrier development during gestation.
abstract: The regulation of epidermal ontogenesis is a complex process. Previous studies have shown that cytokines (IL-1, TNFalpha and IL-6) regulate permeability barrier homeostasis in adult mice. Recently, we reported that IL-1 and TNFalpha accelerate stratum corneum (SC) formation and permeability barrier development in foetal rodents. Here, we determined whether IL-6 also regulates SC formation and permeability barrier development during late gestation. Using a rat skin explant model, we demonstrated that IL-6 accelerates permeability barrier formation in a time- and dose-dependent fashion. This acceleration of barrier formation is attributable to (a) accelerated lamellar membrane maturation, (b) formation of a multi-layer SC and (c) enhanced expression of epidermal differentiation markers. When comparing epidermis of IL-6-deficient (knockout mice) and wild-type foetal mice at days 16-18, we could not detect any abnormalities in either SC formation or the expression of differentiation markers in knockout (KO) mice. In parallel, the basal expression levels of IL-6 mRNA in epidermis and IL-6 protein in amniotic fluid were very low, with only a minimal change in IL-6 receptor mRNA levels in epidermis of days 16-22 foetal mice. These low IL-6 levels may account, at least in part, for the absence of epidermal abnormalities in IL-6 KO mice. In conclusion, exogenous IL-6 accelerates epidermal ontogenesis, but it is not essential for normal epidermal maturation.
authors.affiliation: Metabolism Section, NCIRE, Veterans Affairs Medical Center, San Francisco, CA 94121, USA. 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: Debbie
authors.initials: D
authors.lastname: Crumrine
authors.forename: Peter M
authors.initials: PM
authors.lastname: Elias
authors.forename: Kenneth R
authors.initials: KR
authors.lastname: Feingold
mesh_terms: D000818:Animals; D002463:Cell Membrane Permeability / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005260:Female; D005333:Fetus / Q000187:drug effects* / Q000378:metabolism; D006706:Homeostasis / Q000187:drug effects / Q000502:physiology; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D023421:Models, Animal; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012867:Skin / Q000187:drug effects* / Q000196:embryology* / Q000378:metabolism; D013997:Time Factors
chemical_list: D015850:Interleukin-6; D012333:RNA, Messenger