Biologically active, alternatively processed interleukin-1 beta in psoriatic scales.
The aims of the present work were to elucidate the biochemical properties of interleukin-1 beta (IL-1 beta) in psoriatic scales to get information on the processing of epidermal IL-1 beta in psoriasis, and to elucidate whether the IL-1 beta in psoriatic scales possesses biological activity. By means of ion exchange chromatography, IL-1 beta in extracts of psoriatic scales was purified to a stage where it could be analyzed with electrophoretic methods and immunoblotting. Compared to mature recombinant human IL-1 beta (Ala 117 IL-1 beta), IL-1 beta in psoriatic scales had a slightly higher apparent molecular mass and a more acidic isoelectric point, as revealed by two-dimensional electrophoresis under denaturing conditions. Isoelectric focusing under non-denaturing conditions of IL-1 beta partially purified from psoriatic scales, or from non-inflamed plantar stratum corneum (Nylander Lundqvist, E., Bäck, O. and Egelrud, T., J. Immunol. 1996. 157: 1699), and of mature IL-1 beta, followed by immunoblotting with IL-1 beta-specific antibodies, showed that psoriatic scales contained two components with IL-1 beta-like immunoreactivity which were isoelectric at pH 6.1 and 6.3, respectively. These components could also be detected in extracts of plantar stratum corneum, which also contained small amounts of an IL-1 beta-like component isoelectric at pH 6.9. Mature IL-1 beta was isoelectric at pH 6.9. No IL-1 beta-like biological activity could be detected in crude extracts of psoriatic scales. These extracts also contained high amounts of IL-1 receptor antagonist. Partially purified preparations of IL-1 beta from psoriatic scales, in which an apparently total separation of IL-1 beta and IL-1 receptor antagonist had been achieved, could induce expression of E-selectin in human umbilical vein endothelial cells. This activity was inhibited by antibodies specific for IL-1 beta, but not by antibodies specific for IL-1 alpha. It is concluded that psoriatic scales contain biologically active IL-1 beta, which has been processed by a mechanism which may be similar to that present in non-inflamed plantar stratum corneum, and which does not involve IL-1 beta converting enzyme.
Lundqvist
E N
EN
Department of Dermatology, Umeå University, Sweden.
Egelrud
T
T
D001681:Biological Assay; D015153:Blotting, Western; D010450:Endopeptidases / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D011565:Psoriasis / Q000276:immunology*; D012795:Sialoglycoproteins / Q000378:metabolism; D012867:Skin / Q000737:chemistry / Q000378:metabolism
C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D012795:Sialoglycoproteins; D010450:Endopeptidases