Published online before print February 8, 2008

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(Journal of Leukocyte Biology. 2008;83:1267-1276.)
© 2008 by Society for Leukocyte Biology

Natural killer cells from protein kinase C ^–/– mice stimulated with interleukin-12 are deficient in production of interferon-

Karen M. Page^*,, Divya Chaudhary, Samuel J. Goldman and Marion T. Kasaian^,1

^* Department of Pharmacology and Experimental Therapeutics, Boston University School of Medicine, Boston, Massachusetts; USA; and
Department of Inflammation, Wyeth Research, Cambridge, Massachusetts, USA

¹Correspondence: Wyeth Research, 200 Cambridge Park Dr., Cambridge, MA 02140, USA. E-mail: mkasaian{at}wyeth.com

Protein kinase C (PKC) is expressed in NK cells, but its functional role has not been defined. Here, we demonstrate involvement of PKC in IL-12-induced NK cell IFN- production. NK cells from PKC^–/– mice produced less IFN- in response to IL-12 than those from wild-type (WT) mice. IL-12-induced NK cell cytotoxicity was unaffected, and NK cells from PKC^–/– mice did not display reduced IFN- production in response to IL-18, indicating a specific role for PKC in IL-12-induced IFN- production. Under the conditions tested, T cells did not produce IFN- in response to IL-12 or affect the ability of NK cells to produce the cytokine. PKC deficiency did not affect NK cell numbers, granularity, viability, or cytotoxic activity in response to polyinosinic:polycytydylic acid. NK cells from PKC^–/– mice exhibited normal expression of IL-12Rβ1 and STAT4 proteins and normal induction of STAT4 phosphorylation in response to IL-12. Phosphorylation of threonine 538 within the catalytic domain of PKC was detectable in NK cells from WT mice but was not enhanced by IL-12. Transcription of IFN- increased similarly in NK cells from WT and PKC^–/– mice in response to IL-12, and there was no difference in IFN- mRNA stability. Taken together, these findings indicate a role for PKC in the post-transcriptional regulation of IL-12-induced IFN- production.

Key Words: cytokines • kinases

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