Gurram, Rama Krishna and Kujur, Weshely and Maurya, Sudeep K and Agrewala, J N (2014) Caerulomycin A enhances transforming growth factor-β (TGF-β)-Smad3 protein signaling by suppressing interferon-γ (IFN-γ)-signal transducer and activator of transcription 1 (STAT1) protein signaling to expand regulatory T cells (Tregs). The Journal of biological chemistry, 289 (25). pp. 17515-28. ISSN 1083-351X
Full text not available from this repository. (Request a copy)Abstract
Cytokines play a very important role in the regulation of immune homeostasis. Regulatory T cells (Tregs) responsible for the generation of peripheral tolerance are under the tight regulation of the cytokine milieu. In this study, we report a novel role of a bipyridyl compound, Caerulomycin A (CaeA), in inducing the generation of Tregs. It was observed that CaeA substantially up-regulated the pool of Tregs, as evidenced by an increased frequency of CD4(+) Foxp3(+) cells. In addition, CaeA significantly suppressed the number of Th1 and Th17 cells, as supported by a decreased percentage of CD4(+)/IFN-γ(+) and CD4(+)/IL-17(+) cells, respectively. Furthermore, we established the mechanism and observed that CaeA interfered with IFN-γ-induced STAT1 signaling by augmenting SOCS1 expression. An increase in the TGF-β-mediated Smad3 activity was also noted. Furthermore, CaeA rescued Tregs from IFN-γ-induced inhibition. These results were corroborated by blocking Smad3 activity, which abolished the CaeA-facilitated generation of Tregs. In essence, our results indicate a novel role of CaeA in inducing the generation of Tregs. This finding suggests that CaeA has enough potential to be considered as a potent future drug for the treatment of autoimmunity.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | Immunology; Immunosuppression; Immunotherapy; SMAD Transcription Factor; STAT Transcription Factor; T Cell |
| Depositing User: | Dr. K.P.S.Sengar |
| Date Deposited: | 09 Feb 2015 05:58 |
| Last Modified: | 22 Jul 2015 04:25 |
| URI: | http://crdd.osdd.net/open/id/eprint/1546 |
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