BARRIER DISRUPTION STIMULATES INTERLEUKIN-1-ALPHA EXPRESSION AND RELEASE FROM A PREFORMED POOL IN MURINE EPIDERMIS

Previous studies have shown that barrier disruption increases epiderma l mRNA levels of interleukin-1 alpha. (IL-1 alpha). We used immunohist ochemistry to examine IL-alpha expression in hairless mouse skin under basal conditions and following barrier abrogation, In untreated mice, IL-1 alpha was present in the dermis and nucleated epidermal layers i n a diffuse, generalized pattern, In essential fatty acid deficient mi ce IL-1 alpha was present in all epidermal layers and the dermis, with prominent staining in the stratum corneum, After acute barrier disrup tion with tape-stripping, IL-1 alpha increased in the epidermis and de rmis within 10 min, remained elevated at 2 and 4 h, and decreased to n ear basal levels by 24 h, Moreover, intense, perinuclear, basal cell s taining appeared at 10 min, persisting until 4 h after barrier disrupt ion, Since the increase in IL-1 alpha immunostaining after acute barri er abrogation precedes the increase in mRNA, we hypothesized that the IL-1 alpha might derive from a preformed pool, Prolonged occlusion of normal skin, a treatment that specifically reduces epidermal mRNA leve ls of IL-1 alpha, decreased basal immunostaining for IL-1 alpha and bl unted the increase in IL-1 alpha usually seen following barrier disrup tion, Moreover, tape-stripping of skin, maintained ex vivo at 4 degree s C, resulted in increased IL-1 alpha immunostaining within the upper nucleated epidermal layers, as well as release of mature IL-1 alpha in to the medium, as measured by Western blotting and enzyme-linked immun osorbent assay, In addition, the stratum corneum attached to the tape contained IL-1 alpha. These studies show that acute barrier disruption induces both the immediate release and dispersion of IL-1 alpha from a pre-formed, epidermal pool, as well as increased IL-1 alpha synthesi s; both mechanisms are consistent with a role for IL-1 alpha in the re gulation of proinflammatory and homeostatic processes in the skin.