Interleukin‐1β converting enzyme in murine Langerhans cells and epidermal‐derived dendritic cell lines

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Abstract
Interleukin (IL)‐1β plays an essential role in the induction of T cell‐mediated immune responses in skin. Langerhans cells (LC), which constitutively express IL‐1β mRNA, have been assumed to be the primary source of IL‐1β in murine epidermis. The purpose of this study was to determine whether LC express mRNA for the IL‐1β converting enzyme (ICE), a protease that is required for processing pro‐IL‐1β into an active form. Here, we report that both IL‐1β 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‐1β and ICE mRNA, and they secrete relatively large amounts of IL‐1β following lipopolysaccharide (LPS) stimulation. Finally, LPS‐triggered IL‐1β 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‐1β within the epidermis, and suggest that the proinflammatory role of IL‐1β may be regulated pharmacologically by ICE inhibitors in vivo.