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

Previous studies have shown that depletion of Langerhans' cells (LC) from m urine epidermis by the superantigen, staphylococcal enterotoxin A (SEA) inv olves interleukin-1 alpha. (IL-1 alpha) and is inhibitable by agents that b lock G-protein-associated kinases, The purpose of this study was to determi ne whether specific kinase inhibitors block LC depletion by inhibiting IL-1 alpha release and to ascertain whether LC depletion by SEA involves cell m igration. These goals were addressed by measuring the IL-1 alpha release wi thin whole or LC-depleted epidermal cell suspensions in the presence of SEA and/or H-7 tan inhibitor of protein kinase C) or H-8 (an inhibitor of G-pr otein-associated kinases) and by examining the migration of cells with LC m arkers in SEA-treated skin sections. The results suggest that LC depletion by SEA involves migration and that this migration is blocked by protein kin ase inhibitors, at least in part, through inhibition of SEA-induced IL-1 al pha. release by epidermal cells.