Transcriptional Regulation of the Gene, Encoding p40 Subunit of IL-12 and IL-23, in Murine Macrophages

Shakhov AN*/**, Lefgen H*/**, Drutskaya LN*, Kuprash DV***, Nedospasov SA*/***

*IRSP, SAIC Frederick, Frederick, MD, USA; **Institute for Toxicology, ETH and University of Zurich, Switzerland; ***Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia

Russ. J. Immunol. 2001, December, 6 (4), 357-366

Interleukin-12 (IL-12) is an immunomodulatory cytokine with broad spectrum of activities, central of which are stimulation of NK cells, and promoting differentiation of T helper cells towards Th1 phenotype. IL-12 consists of two unrelated subunits, p35 and p40. Recently discovered cytokine, IL-23, which has both unique properties and those overlapping with IL-12, also contains p40 associated with another subunit, p19. Both IL-12 and IL-23 transmit the signal through receptors associated with JAK-STAT pathways. One of the critical components in the control of both IL-12 and IL-23 regulation is the transcriptional control of p40 gene which is induced in macrophages and dendritic cells in response to bacterial endotoxin, IFN-gamma and other stimuli. In the present study we report on the structure of the transcriptional unit of the murine p40 gene, its promoter and inducible expression of p40 in murine macrophages. Our findings are consistent with multi-level regulation of p40 expression.

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