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Anti-inflammatory protein TSG-6 secreted by activated MSCs attenuates zymosan-induced mouse peritonitis by decreasing TLR2/NF-κB signaling in resident macrophages
Open accessAbstract
Human mesenchymal stem/progenitor cells (hMSCs) repair tissues and modulate immune systems but the mechanisms are not fully understood. We demonstrated that hMSCs are activated by inflammatory signals to secrete the anti-inflammatory protein, TNF-α–stimulated gene 6 protein (TSG-6) and thereby create a negative feedback loop that reduces inflammation in zymosan-induced peritonitis. The results demonstrate for the first time that TSG-6 interacts through the CD44 receptor on resident macrophages to decrease zymosan/TLR2-mediated nuclear translocation of the NF-κB. The negative feedback loop created by MSCs through TSG-6 attenuates the inflammatory cascade that is initiated by resident macrophages and then amplified by mesothelial cells and probably other cells of the peritoneum. Because inflammation underlies many pathologic processes, including immune responses, the results may explain the beneficial effects of MSCs and TSG-6 in several disease models.
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Dominici, M., Le Blanc, K., Mueller, I., Slaper-Cortenbach, I., Marini, F. C., Krause, D. S., Deans, R. J., Keating, A., Prockop, D. J., & Horwitz, E. M. (2006) · Cytotherapy · doi:10.1080/14653240600855905 · Cited by 17,766
Self-citationMesenchymal stem cells as trophic mediators
Caplan, A. I., & Dennis, J. E. (2006) · Journal of Cellular Biochemistry · doi:10.1002/jcb.20886 · Cited by 2,992
Németh, K., Leelahavanichkul, A., Yuen, P. S. T., Mayer, B., Parmelee, A., Doi, K., Robey, P. G., Leelahavanichkul, K., Koller, B. H., Brown, J. M., et al. (2009) · Nature Medicine · doi:10.1038/nm.1905 · Cited by 2,364
Phagocyte partnership during the onset and resolution of inflammation
Soehnlein, O., & Lindbom, L. (2010) · Nature Reviews Immunology · doi:10.1038/nri2779 · Cited by 1,054
Cited by
Transcriptome-Based Network Analysis Reveals a Spectrum Model of Human Macrophage Activation
Xue, J., Schmidt, S. V., Sander, J., Draffehn, A., Krebs, W., Quester, I., De Nardo, D., Gohel, T. D., Emde, M., Schmidleithner, L., et al. (2014) · Immunity · doi:10.1016/j.immuni.2014.01.006 · Cited by 2,210
Mesenchymal stem cell perspective: cell biology to clinical progress
Pittenger, M. F., Discher, D. E., Péault, B. M., Phinney, D. G., Hare, J. M., & Caplan, A. I. (2019) · npj Regenerative Medicine · doi:10.1038/s41536-019-0083-6 · Cited by 2,008
Immunoregulatory mechanisms of mesenchymal stem and stromal cells in inflammatory diseases
Shi, Y., Wang, Y., Li, Q., Liu, K., Hou, J., Shao, C., & Wang, Y. (2018) · Nature Reviews Nephrology · doi:10.1038/s41581-018-0023-5 · Cited by 1,223
Multipotent mesenchymal stromal cells and the innate immune system
Le Blanc, K., & Mougiakakos, D. (2012) · Nature Reviews Immunology · doi:10.1038/nri3209 · Cited by 1,018
Mechanisms of mesenchymal stem/stromal cell function
Spees, J. L., Lee, R. H., & Gregory, C. A. (2016) · Stem Cell Research & Therapy · doi:10.1186/s13287-016-0363-7 · Cited by 891
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Metadata
- Authors
- Choi, H., Lee, R. H., Bazhanov, N., Oh, J. Y., & Prockop, D. J.
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2011-07-14
- Volume
- 118
- Issue
- 2
- Pages
- 330-338
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W2028702444
- Cited by
- 637
- References
- 4
- FWCI
- 15.31
- Type
- journal article
- Language
- en
- Open access
- green
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- Choi, H., Lee, R. H., Bazhanov, N., Oh, J. Y., & Prockop, D. J. (2011). Anti-inflammatory protein TSG-6 secreted by activated MSCs attenuates zymosan-induced mouse peritonitis by decreasing TLR2/NF-κB signaling in resident macrophages. Blood. https://doi.org/10.1182/blood-2010-12-327353
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