Interleukin‐2 activates nuclear phospholipase‐Cβ by mitogen‐activated protein kinase‐dependent phosphorylation in human natural killer cells

2001 ◽  
Vol 15 (10) ◽  
pp. 1789-1791 ◽  
Author(s):  
Marco Vitale ◽  
Alessandro Matteucci ◽  
Lucia Manzoli ◽  
Luigi Rodella ◽  
Adriana R. Mariani ◽  
...  
Blood ◽  
2005 ◽  
Vol 105 (1) ◽  
pp. 282-288 ◽  
Author(s):  
Athanasios Mavropoulos ◽  
Gareth Sully ◽  
Andrew P. Cope ◽  
Andrew R. Clark

Abstract The rapid induction of interferon-γ (IFN-γ) by innate cytokines such as interleukin 12 (IL-12) and IL-18 is critical for immunity against infectious pathogens. We investigated the molecular mechanisms underlying this response. IL-12 and IL-18 rapidly and synergistically induced the secretion of IFN-γ by freshly purified human peripheral blood lymphocytes. At early time points, IFN-γ was expressed almost exclusively by natural killer cells and in both CD56bright and CD56dim subpopulations. Mitogen-activated protein kinase p38 was activated strongly by IL-18 and weakly by IL-12 in natural killer cells but was not activated by either cytokine in T cells. The expression of IFN-γ mRNA and protein was dose-dependently blocked by SB203580, a specific inhibitor of mitogen-activated protein kinase p38, which also caused a dramatic destabilization of IFN-γ mRNA. The 3′ untranslated region (UTR) of IFN-γ mRNA conferred p38 responsiveness to a heterologous reporter mRNA. Therefore, the synergistic induction of IFN-γ by IL-12 and IL-18 in natural killer cells is mediated at least in part by p38-dependent and 3′ UTR-mediated stabilization of IFN-γ mRNA. (Blood. 2005;105:282-288)


1992 ◽  
Vol 22 (1) ◽  
pp. 1-6 ◽  
Author(s):  
Daniel M. Baume ◽  
Michael J. Robertson ◽  
Herbert Levine ◽  
Thomas J. Manley ◽  
Peter W. Schow ◽  
...  

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