IL-6 stimulates but is not essential for stratum corneum formation and permeability barrier development during gestation

Exp Dermatol. 2010 Aug;19(8):e31-6. doi: 10.1111/j.1600-0625.2009.00968.x.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Cell Membrane Permeability / drug effects*
  • Cell Membrane Permeability / physiology
  • Dose-Response Relationship, Drug
  • Female
  • Fetus / drug effects*
  • Fetus / metabolism
  • Homeostasis / drug effects
  • Homeostasis / physiology
  • Interleukin-6 / genetics
  • Interleukin-6 / metabolism
  • Interleukin-6 / pharmacology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Models, Animal
  • Pregnancy
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Skin / drug effects*
  • Skin / embryology*
  • Skin / metabolism
  • Time Factors

Substances

  • Interleukin-6
  • RNA, Messenger