Ca2+/calmodulin-dependent kinase kinase α is expressed by monocytic cells and regulates the activation profile

Christopher B. Guest, Eric L. Deszo, Matthew E. Hartman, Jason M. York, Keith W. Kelley, Gregory G. Freund

    Research output: Contribution to journalArticlepeer-review

    Abstract

    Macrophages are capable of assuming numerous phenotypes in order to adapt to endogenous and exogenous challenges but many of the factors that regulate this process are still unknown. We report that Ca2+/calmodulin-dependent kinase α (CaMKKα) is expressed in human monocytic cells and demonstrates that its inhibition blocks type-II monocytic cell activation and promotes classical activation. Affinity chromatography with paramagnetic beads isolated an approximately 50 kDa protein from nuclear lysates of U937 human monocytic cells activated with phorbol-12-myristate-13 acetate (PMA). This protein was identified as CaMKKα by mass spectrometry and Western analysis. The function of CaMKKα in monocyte activation was examined using the CaMKKα inhibitors (STO-609 and forskolin) and siRNA knockdown. Inhibition of CaMKKα, enhanced PMA-dependent CD86 expression and reduced CD11b expression. In addition, inhibition was associated with decreased translocation of CaMKKα to the nucleus. Finally, to further examine monocyte activation profiles, TNFα and IL-10 secretion were studied. CaMKKα inhibition attenuated PMA-dependent IL-10 production and enhanced TNFα production indicating a shift from type-II to classical monocyte activation. Taken together, these findings indicate an important new role for CaMKKα in the differentiation of monocytic cells.

    Original languageEnglish (US)
    Article numbere1606
    JournalPloS one
    Volume3
    Issue number2
    DOIs
    StatePublished - Feb 13 2008

    ASJC Scopus subject areas

    • General

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