Interleukin-1 beta converting enzyme in murine Langerhans cells and epidermal-derived dendritic cell lines

Interleukin (IL)-1 beta plays an essential role in the induction of T cell-mediated immune responses in skin. Langerhans cells (LC), which constitutively express IL-1 beta mRNA, have been assumed to be the primary source of IL-1 beta in murine epidermis. The purpose of this study was to determine whether LC express mRNA for the IL-1 beta converting enzyme (ICE), a protease that is required for processing pro-IL-1 beta into an active form. Here, we report that both IL-1 beta and ICE mRNA are expressed by the Ia+ population (i.e. LC) in murine epidermis. Moreover, murine epidermal-derived DC lines (XS series) also express both IL-1 beta and ICE mRNA, and they secrete relatively large amounts of IL-1 beta following lipopolysaccharide (LPS) stimulation. Finally, LPS-triggered IL-1 beta secretion by XS cells is blocked almost completely by the ICE inhibitor acetyl-Tyr-Val-Ala-Asp-CH2OC(O)-[2,6-(CF3)2]Ph. These results demonstrate that LC are the primary source of IL-1 beta within the epidermis, and suggest that the proinflammatory role of IL-1 beta may be regulated pharmacologically by ICE inhibitors in vivo.