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Rahim, S.S. and Khan, N. and Boddupalli, C.S. and Hasnain, S.E. and Mukhopadhyay, Sangita (2005) Interleukin-10 (IL-10) mediated suppression of IL-12 production in RAW 264.7 cells also involves c-rel transcription factor. Immunology, 114 (3). pp. 313-321. ISSN 0019-2805

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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-kappaB (NF-kappaB). 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 (IkappaBalpha) in the cytoplasm, indicating that IL-10 prevents degradation of IkappaBalpha 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-kappaB could not rescue the inhibitory effect of IL-10 on IL-12 production, suggesting that NF-kappaB 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.

Item Type: Article
Depositing User: Dr P Divakar
Date Deposited: 01 Jul 2015 09:30
Last Modified: 01 Jul 2015 09:30
URI: http://cdfd.sciencecentral.in/id/eprint/208

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