Premium
Natural killer cells from protein kinase C θ −/− mice stimulated with interleukin‐12 are deficient in production of interferon‐γ
Author(s) -
Page Karen M.,
Chaudhary Divya,
Goldman Samuel J.,
Kasaian Marion T.
Publication year - 2008
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.1107745
Subject(s) - protein kinase c , biology , interleukin 12 , interleukin 21 , cytotoxic t cell , cytokine , stat4 , interleukin 15 , microbiology and biotechnology , lymphokine activated killer cell , kinase , interleukin , phosphorylation , immunology , in vitro , biochemistry , stat3 , stat
Protein kinase C θ (PKCθ) is expressed in NK cells, but its functional role has not been defined. Here, we demonstrate involvement of PKCθ in IL‐12‐induced NK cell IFN‐γ production. NK cells from PKCθ −/− mice produced less IFN‐γ in response to IL‐12 than those from wild‐type (WT) mice. IL‐12‐induced NK cell cytotoxicity was unaffected, and NK cells from PKCθ −/− mice did not display reduced IFN‐γ production in response to IL‐18, indicating a specific role for PKCθ in IL‐12‐induced IFN‐γ production. Under the conditions tested, T cells did not produce IFN‐γ in response to IL‐12 or affect the ability of NK cells to produce the cytokine. PKCθ deficiency did not affect NK cell numbers, granularity, viability, or cytotoxic activity in response to polyinosinic:polycytydylic acid. NK cells from PKCθ −/− 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 PKCθ was detectable in NK cells from WT mice but was not enhanced by IL‐12. Transcription of IFN‐γ increased similarly in NK cells from WT and PKCθ −/− mice in response to IL‐12, and there was no difference in IFN‐γ mRNA stability. Taken together, these findings indicate a role for PKCθ in the post‐transcriptional regulation of IL‐12‐induced IFN‐γ production.