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.
Ariizumi
K
K
Department of Dermatology, University of Texas Southwestern Medical Center, Dallas 75235, USA.
Kitajima
T
T
Bergstresser
O R
OR
Takashima
A
A
D000818:Animals; D001483:Base Sequence; D020170:Caspase 1; D002460:Cell Line; D003546:Cysteine Endopeptidases / Q000096:biosynthesis* / Q000235:genetics; D003713:Dendritic Cells / Q000201:enzymology / Q000378:metabolism; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000235:genetics; D007375:Interleukin-1 / Q000235:genetics / Q000378:metabolism; D007801:Langerhans Cells / Q000201:enzymology*; D008264:Macrophages; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000032:analysis
D000949:Histocompatibility Antigens Class II; D007375:Interleukin-1; D012333:RNA, Messenger; D003546:Cysteine Endopeptidases; D020170:Caspase 1