IL-32θ negatively regulates IL-1β production through its interaction with PKCδ and the inhibition of PU.1 phosphorylation

It has been well known that IL-32 exerts pro-inflammatory effects on the various inflammatory diseases in clinical studies. Here, we confirmed that IL-32 theta, a new isoform of IL-32, decreased the phorbol 12-myristate 13-acetate (PMA)-induced IL-1 beta expression in THP-1 human myelomonocyte. We previously reported that the IL-32 isoforms control expressions of other cytokines via novel PKCs. Likewise, IL-32 theta interacted with PKC delta, and consequently inhibited PKC delta-mediated phosphorylation of PU.1. Moreover, IL-32 theta attenuated the localization of PU.1 into the IL-1 beta promoter region. These findings reveal that IL-32 theta reduces PKC delta-mediated phosphorylation of PU.1, resulting in attenuation of IL-1 beta production. Structured summary of protein interactions: IL-32 theta physically interacts with PKC delta by anti tag coimmunoprecipitation (1, 2) IL-32 theta physically interacts with PKC epsilon by anti tag coimmunoprecipitation (1, 2) PKC delta physically interact with PU.1 by anti tag coimmunoprecipitation (View interaction) (C) 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.