ORIGINAL ARTICLE: Interleukin-10 (IL-10) mediated suppression of IL-12 production in RAW 264.7 cells also involves c-rel transcription factor

• Published in: Immunology Vol. 114; no. 3; pp. 313 - 321
• Main Authors: Rahim, Sheikh Showkat, Khan, Nooruddin, Boddupalli, Chandra Sekhar, Hasnain, Seyed E, Mukhopadhyay, Sangita
• Format: Journal Article
• Language: English
• Published: 01.03.2005
• ISSN: 0019-2805; 1365-2567
• DOI: 10.1111/j.1365-2567.2005.02107.x

Interleukin-10 (IL-10) is known to inhibit IL-12 production in macrophages primarily at the transcriptional level with the involvement of p50 and p65 nuclear factor- Kappa B (NF- Kappa B). We demonstrate that the c-rel transcription factor also plays a major role in IL-10-mediated IL-12 suppression. Treatment of macrophages with recombinant IL-10 inhibited nuclear c-rel levels, whereas addition of neutralizing anti-IL-10 antibody up-regulated both nuclear c-rel levels and IL-12 production by macrophages. Decreased nuclear c-rel was associated with a reduction in phosphorylation of inhibitory kappa B alpha (I Kappa B alpha ) in the cytoplasm, indicating that IL-10 prevents degradation of I Kappa B alpha and the subsequent translocation of c-rel into the nucleus. Treatment with leptomycin B, a known inhibitor of c-rel at a concentration of 10 nm, when used with anti-IL-10 antibody, resulted in reduced expression of IL-12. In a complementary experiment, in vitro transient expression of p65 NF- Kappa B could not rescue the inhibitory effect of IL-10 on IL-12 production, suggesting that NF- Kappa B alone was not sufficient to restore IL-12 production during IL-10 treatment. However, over-expression of c-rel resulted in IL-12 restoration upon stimulation with lipopolysaccharide plus interferon- gamma during IL-10 treatment. Our studies highlight the involvement of c-rel in IL-10-mediated IL-12 regulation.