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ISSN - 20790597, EISSN - 20790600, Russian Journal of Genetics: Applied Research, 2013, vol. 4, p. 568-574

Dynamics of IL-12 cytokine expression in human macrophages after dioxin exposure

Oshchepkov D. Y., Kashina E. V., Antontseva E. V., Oshchepkova E. A., Mordvinov V. A., Furman D. P.

© 2014, Pleiades Publishing, Ltd. Interleukin IL-12 is a key proinflammatory cytokine synthesized by macrophages; however, information on the effect of dioxin on its expression is still fragmentary. The presence of previously identified potential dioxin-responsive elements (DREs) in the regulatory regions of IL12A and IL12B genes, encoding IL-12 subunits IL-12p35 and IL-12p40, respectively, suggests direct activation of these genes by binding of the dioxin/AhR/ARNT complex to DREs. In this work the binding capacity of these DREs was demonstrated by gel shift assay. The study of the dynamics of IL12A and IL12B gene expression in the human U937 macrophages revealed no influence of dioxin on IL12A expression. In contrast, activation of IL12B gene expression with subsequent inhibition was noted. The observed dynamics can be explained by direct activation of the expression by the dioxin-containing complex and subsequent inhibition of the expression as a result of oxidative stress caused by dioxin. Thus, the well-known effect of dioxin on the immune system can be associated with its differential influence on the expression dynamics of the genes encoding IL-12 subunits.