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.