I?B? augments IL-12- and IL-18-mediated IFN-? production in human NK cells.

ABSTRACT: Interferon-? (IFN-?) production by natural killer (NK) cells and cytotoxic lymphocytes is a key component of innate and adaptive immune responses. Because inhibitor of ?B-? (I?B?), a Toll-like receptor (TLR)/interleukin-1 receptor (IL-1R) inducible transcription factor, regulates IFN-? production in KG-1 cells, we tested I?B?'s role in the classic lymphocyte pathway of IL-12/IL-18-induced IFN-?. Upon stimulation with IL-12/IL-18, monocyte-depleted human peripheral blood lymphocytes expressed the 79-kDa form of I?B? and released IFN-?. CD56(+) NK cells were shown to be the I?B?-producing lymphocyte subpopulation, which also released abundant IFN-? in response to IL-12/IL-18. Importantly, I?B? was undetectable in CD56(-) lymphocytes where IFN-? release was 10-fold lower. In addition, small interfering RNA knockdown of I?B? suppressed IFN-? expression in CD56(+) cells. The association of I?B? with the IFN-? promoter was documented by chromatin immunoprecipitation. IFN-? promoter activity from I?B? overexpression was confirmed by luciferase reporter assay. Finally, I?B? coprecipitated with p65 and p50 NF-?B in NK cells in response to IL-12/IL-18, suggesting that I?B?'s effects on IFN-? promoter activity are coregulated by NF-?B. These results suggest that I?B? functions as an important regulator of IFN-? in human NK cells, further expanding the class of I?B?-modulated genes.

SUBMITTER: Kannan Y 

PROVIDER: S-EPMC3062297 | biostudies-other | 2011 Mar

REPOSITORIES: biostudies-other