IL-1 beta activation in human epidermis.
IL-1 beta is produced as an inactive 31-kDa precursor processed to active 18-kDa IL-1 beta by proteolytic cleavage, catalyzed by the highly specific IL-1-converting enzyme (ICE). In vitro activation of IL-1 beta can also be obtained by other proteases. Human keratinocytes express IL-1 beta, but not active ICE. The role played by IL-1 beta produced by keratinocytes has therefore been unclear. We asked whether normal human plantar stratum corneum contains biologically active IL-1 beta and, if so, by which mechanism this IL-1 beta is activated. Crude extracts and partially purified preparations from which IL-1 alpha had been removed were used. Biologic IL-1 activity was measured as the ability to induce expression of E-selectin in HUVEC. The crude extract contained IL-1-like activity that could be partially abolished with Abs to IL-1 alpha or IL-1 beta and totally inhibited with a mixture of the two Abs. IL-1 activity in the partially purified preparation was totally inhibited by Abs to IL-1 beta. The specific IL-1 beta activity in the two preparations was 60 to 85% of the sp. act. of recombinant human IL-1 beta. IL-1 beta from plantar stratum corneum had a slightly higher molecular mass than recombinant mature IL-1 beta. Its isoelectric point was approximately 6.1 compared with 6.9 for rIL-1 beta. We conclude that human plantar stratum corneum contains biologically active IL-1 beta that has been activated by an alternative mechanism that does not involve ICE. This is, to our knowledge, the first report of an alternative mechanism of IL-1 beta activation occurring in vivo.
Nylander-Lundqvist
E
E
Department of Dermatology and Venereology, University Hospital, Umea, Sweden.
Bäck
O
O
Egelrud
T
T
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D020170:Caspase 1; D003546:Cysteine Endopeptidases / Q000378:metabolism; D019040:E-Selectin / Q000096:biosynthesis; D010450:Endopeptidases / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D004817:Epidermis / Q000378:metabolism*; D005528:Foot; D006801:Humans; D007375:Interleukin-1 / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology; D007526:Isoelectric Point; D015603:Keratinocytes / Q000378:metabolism*; D008969:Molecular Sequence Data; D008970:Molecular Weight; D011498:Protein Precursors / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D011994:Recombinant Proteins / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D019040:E-Selectin; D007375:Interleukin-1; D011498:Protein Precursors; D011994:Recombinant Proteins; D010450:Endopeptidases; D003546:Cysteine Endopeptidases; D020170:Caspase 1