Interleukin-1alpha gene expression during wound healing.

Interleukin-1alpha is known to be constitutively produced by epidermal keratinocytes under normal conditions, and injection of this cytokine enhances wound reepithelialization. However, no studies have characterized the temporal sequence of interleukin-1alpha gene expression over the time course of wound healing, and the cellular sources of this cytokine have not been identified. In the present studies, levels of interleukin-1alpha messenger RNA in wound tissue isolated from SKH-1 hairless mice were characterized and the cells that produced interleukin-1alpha immunoreactive protein over a 10-day time course of wound healing were defined. A time-dependent upregulation in interleukin-1alpha gene expression occurred immediately (4 hours) after a full-thickness wound was made, which represented a four-fold increase over levels of cytokine gene expression detected in nonwounded skin. Upregulation of cytokine gene expression correlated with an immediate increase in plasma interleukin-1alpha levels and was followed by an increase in interleukin-1alpha immunoreactive protein localized to keratinocytes within the leading edge of the wound and epidermis, as well as to neutrophils within the dermis. The rapid increase in local and systemic interleukin-1alpha levels correlated with the infiltration of a significant number of neutrophils into the wound site and with the proliferation of both basal keratinocytes and dermal fibroblasts. Given the known ability of interleukin-1alpha to regulate proliferation and migration of epidermal keratinocytes and to indirectly induce leukocyte chemotaxis, the results of the present studies suggest that interleukin-1alpha may be an important cytokine with both local and systemic actions that are linked to the initiation of critical cellular events early in wound healing.