Barrier Disruption Stimulates Interleukin-1 Alpha Expression and Release from a Pre-formed Pool in Murine Epidermis

Previous studies have shown that barrier disruption increases epidermal mRNA levels of interleukin-1 alpha (IL-1 alpha). We used immunohistochemistry to examine IL-1 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 in a diffuse, generalized pattern. In essential fatty acid deficient mice IL-1 alpha was present in all epidermal layers and the dermis, with prominent staining in the stratum corneum. After acute barrier disruption with tape-stripping, IL-1 alpha increased in the epidermis and dermis within 10 min, remained elevated at 2 and 4 h, and decreased to near basal levels by 24 h. Moreover, intense, perinuclear, basal cell staining appeared at 10 min, persisting until 4 h after barrier disruption. Since the increase in IL-1 alpha immunostaining after acute barrier abrogation precedes the increase in mRNA, we hypothesized that the IL-1 alpha might derive from a pre-formed pool. Prolonged occlusion of normal skin, a treatment that specifically reduces epidermal mRNA levels of IL-1 alpha, decreased basal immunostaining for IL-1 alpha and blunted the increase in IL-1 alpha usually seen following barrier disruption. Moreover, tape-stripping of skin, maintained ex vivo at 4 degrees C, resulted in increased IL-1 alpha immunostaining within the upper nucleated epidermal layers, as well as release of mature IL-1 alpha into the medium, as measured by Western blotting and enzyme-linked immunosorbent 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 synthesis; both mechanisms are consistent with a role for IL-1 alpha in the regulation of proinflammatory and homeostatic processes in the skin.