Open Access

The influence of JNK and P38 MAPK inhibition on IL-12P40 and IL-23 production depending on IL12B promoter polymorphism

  • Zlatka Georgieva Dobreva1Email author,
  • Spaska Angelova Stanilova1 and
  • Lyuba Dineva Miteva1
Cellular & Molecular Biology LettersAn International Journal200914:22

DOI: 10.2478/s11658-009-0022-4

Received: 2 December 2008

Accepted: 4 June 2009

Published: 25 June 2009

Abstract

The interleukin-12p40 gene (IL12B) encodes the p40 polypeptide chain, which, together with p19, composes IL-23. A bi-allelic promoter polymorphism (IL12Bpro) located at −2703 bp of the transcription initiation site has been reported to show associations with IL-12p40 production. To elucidate the dependence of IL-12p40 and IL-23 production on IL12Bpro polymorphism in relation to MAPK signal transduction pathways, we examined the effect of JNK and p38 inhibition on the secretion of these cytokines by stimulated peripheral blood mononuclear cells (PBMC) from healthy donors with 1.1 and 1.2/2.2 IL12Bpro genotypes. Stimulation with LPS and C3bgp resulted in approximately equal IL-12p40 production from PBMC with the 1.1 and 1.2/2.2 genotypes. The inhibition of JNK and p38 before stimulation significantly upregulated IL-12p40 production by PBMC with the 1.1 genotype, but did not influence IL-12p40 production from PBMC with the 1.2/2.2 genotype. Cultures of PBMC with the 1.1 genotype produced significantly more IL-12p40 than PBMC with the 1.2/2.2 genotype after stimulation with PHA. Inhibition of p38 kinase upregulated p40 production only in cultures with the 1.1 genotype. Decreased IL-23 production was observed in C3bgp-stimulated cultures after the inhibition of p38 regardless of the genotype of the tested cells. We concluded that IL-12p40 and IL-23 expression, which is mediated by the p38 and JNK intracellular signaling pathways, is influenced by IL12Bpro polymorphism.

Key words

IL-12p40 IL-23 IL12B Promoter polymorphism

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