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Lipopolysaccharide-Mediated IL-10 Transcriptional Regulation Requires Sequential Induction of Type I IFNs and IL-27 in Macrophages
Open accessAbstract
IL-10 is a potent anti-inflammatory molecule that regulates excessive production of inflammatory cytokines during an infection or tissue damage. Dysregulation of IL-10 is associated with a number of autoimmune diseases, and so, understanding the mechanisms by which IL-10 gene expression is regulated remains an important area of study. Macrophages represent a major source of IL-10, which is generated in response to TLR signaling as a feedback mechanism to curtail inflammatory response. In this study, we identify a signaling pathway in murine bone marrow-derived macrophages in which activation of TLR4 by LPS induces the expression of IL-10 through the sequential induction of type I IFNs followed by induction and signaling through IL-27. We demonstrate that IL-27 signaling is required for robust IL-10 induction by LPS and type I IFNs. IL-27 leads directly to transcription of IL-10 through the activation of two required transcription factors, STAT1 and STAT3, which are recruited to the IL-10 promoter. Finally, through systematic functional promoter-reporter analysis, we identify three cis elements within the proximal IL-10 promoter that play an important role in regulating transcription of IL-10 in response to IL-27.
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Cites
Toll-like receptors in innate immunity
Takeda, K. (2004) · International Immunology · doi:10.1093/intimm/dxh186 · Cited by 3,328
Stumhofer, J. S., Laurence, A., Wilson, E. H., Huang, E., Tato, C. M., Johnson, L. M., Villarino, A. V., Huang, Q., Yoshimura, A., Sehy, D., et al. (2006) · Nature Immunology · doi:10.1038/ni1376 · Cited by 955
Awasthi, A., Carrier, Y., Peron, J. P. S., Bettelli, E., Kamanaka, M., Flavell, R. A., Kuchroo, V. K., Oukka, M., & Weiner, H. L. (2007) · Nature Immunology · doi:10.1038/ni1541 · Cited by 804
Fitzgerald, D. C., Zhang, G.-X., El-Behi, M., Fonseca-Kelly, Z., Li, H., Yu, S., Saris, C. J. M., Gran, B., Ciric, B., & Rostami, A. (2007) · Nature Immunology · doi:10.1038/ni1540 · Cited by 529
Cited by
The role of IL-10 in immune regulation during M. tuberculosis infection
Redford, P. S., Murray, P. J., & O'Garra, A. (2011) · Mucosal Immunology · doi:10.1038/mi.2011.7 · Cited by 472
The macrophage response towards LPS and its control through the p38MAPK–STAT3 axis
Bode, J. G., Ehlting, C., & Häussinger, D. (2012) · Cellular Signalling · doi:10.1016/j.cellsig.2012.01.018 · Cited by 393
Oishi, Y., Spann, N. J., Link, V. M., Muse, E. D., Strid, T., Edillor, C., Kolar, M. J., Matsuzaka, T., Hayakawa, S., Tao, J., et al. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2016.11.009 · Cited by 342
The Roles of Type I Interferon in Bacterial Infection
Boxx, G. M., & Cheng, G. (2016) · Cell Host & Microbe · doi:10.1016/j.chom.2016.05.016 · Cited by 335
Self-citationmiR-24 Regulates Macrophage Polarization and Plasticity
Afsar R. Naqvi, J. B. F., & Nares, S. (2015) · Journal of Clinical & Cellular Immunology · doi:10.4172/2155-9899.1000362 · Cited by 65
Metadata
- Authors
- Iyer, S. S., Ghaffari, A. A., & Cheng, G.
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2010-12-01
- Volume
- 185
- Issue
- 11
- Pages
- 6599-6607
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W2108830583
- Cited by
- 193
- References
- 4
- FWCI
- 3.70
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Iyer, S. S., Ghaffari, A. A., & Cheng, G. (2010). Lipopolysaccharide-Mediated IL-10 Transcriptional Regulation Requires Sequential Induction of Type I IFNs and IL-27 in Macrophages. The Journal of Immunology. https://doi.org/10.4049/jimmunol.1002041
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