Effect of a Small Selective Inhibitor of C-Jun N-Terminal Kinase on the Inducible mRNA Expression of Interleukin-6 and Interleukin-18.

Background: The expression of many inducible genes, involved in cell growth and differentiation as cytokine genes are regulated by receptor-activated intracellular signalling pathways, including the c-Jun N-terminal kinase (JNK) mitogen-activated protein kinase pathway.

Aim: We examined the involvement of the JNK signalling pathway in the regulation of the inducible interleukin-6 (IL-6) and interleukin-18 (IL-18) gene expression at the transcriptional level.

Methods: Peripheral blood mononuclear cells (PBMC) from healthy donors were stimulated with lipopolysaccharide (LPS) and C3 binding glycoprotein (C3bgp) with or without SP600125 and cultured for 6 h. After mRNA isolation, a qRT-PCR was performed.

Results: Regarding IL-6 and IL-18 mRNA expression, donors were divided into two groups of high and low responders. SP600125 inhibited significantly IL-6 mRNA transcription in the high responder group and did not influence the transcription level in the low responder group. Concerning IL-18 mRNA, we detect the significant effect of SP600125 on the inducible mRNA in high responder group upon C3bgp stimulation.

Conclusion: JNK transduction pathway is involved in the production of IL-6 mRNA, after LPS and C3bgp stimulation. We suggest that the inhibition of JNK may be beneficial only for higher responding patients during the treatment of inflammatory and autoimmune diseases.