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.
Dobreva
Zlatka Georgieva
ZG
Department of Molecular Biology, Immunology & Genetics, Faculty of Medicine, Trakia University, Armeiska 11, 6000 Stara Zagora, Bulgaria. zdobreva@mf.uni-sz.bg
Stanilova
Spaska Angelova
SA
Miteva
Lyuba Dineva
LD
D002478:Cells, Cultured; D004926:Escherichia coli; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D053762:Interleukin-12 Subunit p40 / Q000096:biosynthesis* / Q000235:genetics*; D053759:Interleukin-23 / Q000096:biosynthesis* / Q000235:genetics*; D048670:MAP Kinase Kinase 4 / Q000502:physiology*; D020935:MAP Kinase Signaling System / Q000502:physiology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000502:physiology*
D053762:Interleukin-12 Subunit p40; D053759:Interleukin-23; D048051:p38 Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4