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

• Published in: FEBS letters 2014-08, Vol.588 (17), p.2822-2829
• Main Authors: Kim, Man Sub, Kang, Jeong-Woo, Lee, Dong Hun, Bak, Yesol, Park, Yun Sun, Song, Yong-Seok, Ham, Sun Young, Oh, Deok Kun, Hong, Jintae, Yoon, Do-Young
• Format: Article
• Language: English
• Subjects: 5′ Rapid Amplification of cDNA Ends; Enzyme Activation - drug effects; HEK293 Cells; Humans; interferon regulatory factor; Interleukin-1beta - biosynthesis; Interleukin-1beta - genetics; Interleukin-1β; Interleukin-32; Interleukins - metabolism; IRF; lipopolysaccharide; LPS; phorbol 12-myristate 13-acetate; Phorbol Esters - pharmacology; Phosphorylation - drug effects; PKC; PKCδ; PMA; Promoter Regions, Genetic - drug effects; Promoter Regions, Genetic - genetics; Protein Binding - drug effects; protein kinase c; Protein Kinase C-delta - metabolism; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins - metabolism; PU.1; RACE; THP-1; TLR; toll like receptor; Trans-Activators - genetics; Trans-Activators - metabolism; Transcriptional Activation - drug effects
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/j.febslet.2014.06.029

•IL-32θ attenuates IL-1β production.•IL-32θ interacts with PKCδ and PKCε.•The association with PKCδ and IL-32θ inhibit PKCδ-mediated PU.1 activation. 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-32θ, a new isoform of IL-32, decreased the phorbol 12-myristate 13-acetate (PMA)-induced IL-1β expression in THP-1 human myelomonocyte. We previously reported that the IL-32 isoforms control expressions of other cytokines via novel PKCs. Likewise, IL-32θ interacted with PKCδ, and consequently inhibited PKCδ-mediated phosphorylation of PU.1. Moreover, IL-32θ attenuated the localization of PU.1 into the IL-1β promoter region. These findings reveal that IL-32θ reduces PKCδ-mediated phosphorylation of PU.1, resulting in attenuation of IL-1β production. IL-32 thetaphysically interacts with PKC delta by anti tag coimmunoprecipitation (1, 2) IL-32 thetaphysically interacts with PKC epsilon by anti tag coimmunoprecipitation (1, 2) PKC deltaphysically interact with PU.1 by anti tag coimmunoprecipitation (View interaction)