JNK1 and JNK2 differently regulate IL-12 production in THP-1 macrophage cells.

Macrophages play a key role in initiating the innate responses to infection by secreting cytokines such as interleukin-12 (IL-12). This study defined the distinct regulation of lipopolysaccharide (LPS)-mediated IL-12 production by c-jun NH(2)-terminal kinase (JNK)1 and JNK2 isoforms in human macrophages. Knockdown of JNK1 and JNK2 by small interference RNA (siRNA) reduced and enhanced LPS-induced IL-12 p40 production in THP-1 macrophage cells, respectively. The simultaneous knockdown of JNK1 and JNK2 augmented LPS-induced IL-12 production as well as a specific JNK inhibitor. In addition, transfection of siRNA against phosphoinositide 3-kinase (PI3K) p110beta attenuated LPS-induced IL-12 production and JNK1 phosphorylation, while not affecting JNK2 phosphorylation. These findings indicate that JNK1- and JNK2-mediated signaling plays a positive and a negative role, respectively, in LPS-induced IL-12 production and PI3K p110beta controls LPS-induced JNK1 activation, not JNK2 activation, resulting in the positive regulation of IL-12 production in THP-1 macrophage cells. Copyright 2010 Elsevier Ltd. All rights reserved.