Differences in the inducible gene expression and protein production of IL-12p40, IL-12p70 and IL-23: Involvement of p38 and JNK kinase pathways

The proper balance between IL-12p40-related cytokines controls the appearance of normal and pathological Th1 immune responses. In this study, we examined the inducible IL-12p40, IL-12p35 and IL-23p19 mRNA expression and protein production in human peripheral blood mononuclear cells (PBMC) and purified monocytes, isolated from healthy donors. We investigated how JNK and p38 MAPKs inhibitors influenced IL-12p40, IL-12p70 and IL-23 production. The cytokines’ quantity determination was performed by ELISA. qRT-PCR was performed for mRNA transcripts detection. All stimuli tested induced higher level of IL-12p40 and IL-12p19 mRNAs. LPS was the strongest inducer of IL-12p40 mRNA, whereas C3bgp stimulated the highest expression of IL-23p19 mRNA in human monocytes. IL-12p40 and IL-23 protein production observed was increased in the highest level after C3bgp stimulation. The inhibition of both JNK and p38 augmented IL-12p40 production. The inhibition of p38 MAPK downregulated IL-23 production and upregulated IL-12p40 production in stimulated monocytes and PBMC. These results provide evidence that in human monocytes and PBMC p38 MAP kinase activation has an opposite effect on the IL-12p40 and IL-23 expression.