Biologically active, alternatively processed interleukin‐1β in psoriatic scales

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Abstract
The aims of the present work were to elucidate the biochemical properties of interleukin‐1β (IL‐1β) in psoriatic scales to get information on the processing of epidermal IL‐1β in psoriasis, and to elucidate whether the IL‐1β in psoriatic scales possesses biological activity. By means of ion exchange chromatography, IL‐1β 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‐1β (Ala 117 IL‐1β), IL‐1β 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‐1β 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‐1β, followed by immunoblotting with IL‐1β‐specific antibodies, showed that psoriatic scales contained two components with IL‐1β‐like immuno‐reactivity which were isoelectric at pH 6.1 and 6.3, respectively. Theses components could also be detected in extracts of plantar stratum corneum, which also contained small amounts of an IL‐1β‐like component isoelectric at pH 6.9. Mature IL‐1β was isoelectric at pH 6.9. No IL‐1β‐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‐1β from psoriatic scales, in which an apparently total separation of IL‐1β 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‐1β, but not by antibodies specific for IL‐1α. It is concluded that psoriatic scales contain biologically active IL‐1β, 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‐1β converting enzyme.