Rahim, Sheikh Showkat ; Khan, Nooruddin ; Boddupalli, Chandra Sekhar ; Hasnain, Seyed E. ; 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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Official URL: http://onlinelibrary.wiley.com/doi/10.1111/j.1365-...
Related URL: http://dx.doi.org/10.1111/j.1365-2567.2005.02107.x
Abstract
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-κB (NF-κB). 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 (IκBα) in the cytoplasm, indicating that IL-10 prevents degradation of IκBα 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-κB could not rescue the inhibitory effect of IL-10 on IL-12 production, suggesting that NF-κB 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-γ during IL-10 treatment. Our studies highlight the involvement of c-rel in IL-10-mediated IL-12 regulation.
Item Type: | Article |
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Source: | Copyright of this article belongs to John Wiley and Sons, Inc. |
ID Code: | 103517 |
Deposited On: | 09 Mar 2018 10:49 |
Last Modified: | 09 Mar 2018 10:49 |
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