IL-1alpha accelerates stratum corneum formation and improves permeability barrier homeostasis during murine fetal development.

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. OBJECT: 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.
CONCLUSION: IL-1 plays a role in regulating the late stages of SC formation and permeability barrier ontogenesis.