Protein-kinase-specific inhibitors block Langerhans' cell migration by inhibiting interleukin-1α release

Abstract

Previous studies have shown that depletion of Langerhans' cells (LC) from murine epidermis by the superantigen, staphylococcal enterotoxin A (SEA) involves interleukin-1α (IL-1α) and is inhibitable by agents that block G- protein-associated kinases. The purpose of this study was to determine whether specific kinase inhibitors block LC depletion by inhibiting IL-1α release and to ascertain whether LC depletion by SEA involves cell migration. These goals were addressed by measuring the IL-1α release within whole or LC-depleted epidermal cell suspensions in the presence of SEA and/or H-7 (an inhibitor of protein kinase C) or H-8 (an inhibitor of G-protein-associated kinases) and by examining the migration of cells with LC markers in SEA- treated skin sections. The results suggest that LC depletion by SEA involves migration and that this migration is blocked by protein kinase inhibitors, at least in part, through inhibition of SEA-induced IL-1α release by epidermal cells.