The DOI matches its Crossref record; 45 of the 45 references it cites were found in a registry or an index.
Involvement of Suppressor of Cytokine Signaling-3 as a Mediator of the Inhibitory Effects of IL-10 on Lipopolysaccharide-Induced Macrophage Activation
Open accessAbstract
Previous studies have shown that IL-10 can induce the expression of the suppressor of cytokine signaling 3 (SOCS-3) mRNA in human monocytes and neutrophils, suggesting that the capacity of IL-10 to inhibit the expression of LPS-inducible proinflammatory genes may depend on SOCS-3 induction. However, no direct experimental evidence has been provided to support such hypothesis. Herein, we show that stable transfection of SOCS-3 into the mouse macrophage cell line J774 resulted in an inhibition of NO, TNF-α, IL-6, and GM-CSF secretion in response to LPS at levels similar to those exerted by IL-10 in LPS-stimulated wild-type J774. Constitutive SOCS-3 expression also down-regulated the mRNA expression of inducible NO synthase and IL-6 and impaired the production of TNF-α, mainly at a post-transcriptional level. In addition, SOCS-3-transfected cells displayed a constitutive expression of the IL-1R antagonist gene, consistent with the observation that IL-10 enhances IL-1R antagonist mRNA in LPS-stimulated wild-type cells. Furthermore, in peritoneal macrophages harvested from mice carrying heterozygous disruption of the SOCS-3 gene, IL-10 was less effective in repressing LPS-stimulated TNF-α and NO production. Taken together, our data show that SOCS-3 inhibits LPS-induced macrophage activation, strongly supporting the idea that it plays a role in the molecular mechanism by which IL-10 down-modulates the effector functions of LPS-activated macrophages. Finally, we show that forced expression of SOCS-3 significantly suppresses the ability of IL-10 to trigger tyrosine phosphorylation of STAT3. Therefore, SOCS-3 functions both as an LPS signal inhibitor and as a negative feedback regulator of IL-10/STAT3 signaling.
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Cites
Interleukin-10 and the Interleukin-10 Receptor
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Cited by
IL-6 induces an anti-inflammatory response in the absence of SOCS3 in macrophages
Yasukawa, H., Ohishi, M., Mori, H., Murakami, M., Chinen, T., Aki, D., Hanada, T., Takeda, K., Akira, S., Hoshijima, M., et al. (2003) · Nature Immunology · doi:10.1038/ni938 · Cited by 771
Self-citationSOCS1/JAB Is a Negative Regulator of LPS-Induced Macrophage Activation
Kinjyo, I., Hanada, T., Inagaki-Ohara, K., Mori, H., Aki, D., Ohishi, M., Yoshida, H., Kubo, M., & Yoshimura, A. (2002) · Immunity · doi:10.1016/s1074-7613(02)00446-6 · Cited by 630
Self-citationSaid, E. A., Dupuy, F. P., Trautmann, L., Zhang, Y., Shi, Y., El-Far, M., Hill, B. J., Noto, A., Ancuta, P., Peretz, Y., et al. (2010) · Nature Medicine · doi:10.1038/nm.2106 · Cited by 481
The paradoxical role of IL-10 in immunity and cancer
Mannino, M. H., Zhu, Z., Xiao, H., Bai, Q., Wakefield, M. R., & Fang, Y. (2015) · Cancer Letters · doi:10.1016/j.canlet.2015.07.009 · Cited by 473
SOCS3 regulates the plasticity of gp130 signaling
Lang, R., Pauleau, A.-L., Parganas, E., Takahashi, Y., Mages, J., Ihle, J. N., Rutschman, R., & Murray, P. J. (2003) · Nature Immunology · doi:10.1038/ni932 · Cited by 439
Metadata
- Authors
- Berlato, C., Cassatella, M. A., Kinjyo, I., Gatto, L., Yoshimura, A., & Bazzoni, F.
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2002-06
- Volume
- 168
- Issue
- 12
- Pages
- 6404-6411
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W1926521347
- Cited by
- 267
- References
- 45
- FWCI
- 10.56
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Berlato, C., Cassatella, M. A., Kinjyo, I., Gatto, L., Yoshimura, A., & Bazzoni, F. (2002). Involvement of Suppressor of Cytokine Signaling-3 as a Mediator of the Inhibitory Effects of IL-10 on Lipopolysaccharide-Induced Macrophage Activation. The Journal of Immunology. https://doi.org/10.4049/jimmunol.168.12.6404
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