Natural killer cells from protein kinase C theta-/- mice stimulated with interleukin-12 are deficient in production of interferon-gamma.
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.
Page
Karen M
KM
Department of Pharmacology and Experimental Therapeutics, Boston University School of Medicine, Boston, Massachusetts, USA.
Chaudhary
Divya
D
Goldman
Samuel J
SJ
Kasaian
Marion T
MT
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003433:Crosses, Genetic; D016207:Cytokines / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation; D007371:Interferon-gamma / Q000096:biosynthesis / Q000172:deficiency*; D018664:Interleukin-12 / Q000494:pharmacology*; D007378:Interleukins / Q000494:pharmacology; D007527:Isoenzymes / Q000235:genetics*; D007694:Killer Cells, Natural / Q000166:cytology / Q000187:drug effects / Q000201:enzymology / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011493:Protein Kinase C / Q000172:deficiency* / Q000235:genetics; D000074121:Protein Kinase C-theta; D011994:Recombinant Proteins / Q000494:pharmacology; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000201:enzymology / Q000276:immunology; D014158:Transcription, Genetic / Q000187:drug effects
D016207:Cytokines; D007378:Interleukins; D007527:Isoenzymes; D011994:Recombinant Proteins; D018664:Interleukin-12; D007371:Interferon-gamma; C489593:Prkcq protein, mouse; D011493:Protein Kinase C; D000074121:Protein Kinase C-theta