First Author | Page KM | Year | 2008 |
Journal | J Leukoc Biol | Volume | 83 |
Issue | 5 | Pages | 1267-76 |
PubMed ID | 18263766 | Mgi Jnum | J:134459 |
Mgi Id | MGI:3788941 | Doi | 10.1189/jlb.1107745 |
Citation | Page KM, et al. (2008) Natural killer cells from protein kinase C theta-/- mice stimulated with interleukin-12 are deficient in production of interferon-gamma. J Leukoc Biol 83(5):1267-76 |
abstractText | Protein kinase C theta (PKCtheta) is expressed in NK cells, but its functional role has not been defined. Here, we demonstrate involvement of PKCtheta in IL-12-induced NK cell IFN-gamma production. NK cells from PKCtheta(-/-) mice produced less IFN-gamma in response to IL-12 than those from wild-type (WT) mice. IL-12-induced NK cell cytotoxicity was unaffected, and NK cells from PKCtheta(-/-) mice did not display reduced IFN-gamma production in response to IL-18, indicating a specific role for PKCtheta in IL-12-induced IFN-gamma production. Under the conditions tested, T cells did not produce IFN-gamma in response to IL-12 or affect the ability of NK cells to produce the cytokine. PKCtheta deficiency did not affect NK cell numbers, granularity, viability, or cytotoxic activity in response to polyinosinic:polycytydylic acid. NK cells from PKCtheta(-/-) mice exhibited normal expression of IL-12Rbeta1 and STAT4 proteins and normal induction of STAT4 phosphorylation in response to IL-12. Phosphorylation of threonine 538 within the catalytic domain of PKCtheta was detectable in NK cells from WT mice but was not enhanced by IL-12. Transcription of IFN-gamma increased similarly in NK cells from WT and PKCtheta(-/-) mice in response to IL-12, and there was no difference in IFN-gamma mRNA stability. Taken together, these findings indicate a role for PKCtheta in the post-transcriptional regulation of IL-12-induced IFN-gamma production. |