Suppressor of Cytokine Signaling 1 Inhibits IL-10-Mediated Immune Responses
- 1 February 2003
- journal article
- Published by The American Association of Immunologists
- Vol. 170 (3), 1383-1391
- https://doi.org/10.4049/jimmunol.170.3.1383
Abstract
IL-10 has proved to be a key cytokine in regulating inflammatory responses by controlling the production and function of various other cytokines. The suppressor of cytokine signaling (SOCS) gene products are a family of cytoplasmic molecules that are essential mediators for negatively regulating cytokine signaling. It has been previously shown that IL-10 induced SOCS3 expression and that forced constitutive expression of SOCS3 inhibits IL-10/STAT3 activation and LPS-induced macrophage activation. In this report, we show that, in addition to SOCS3 expression, IL-10 induces SOCS1 up-regulation in all cell lines tested, including Ba/F3 pro-B cells, MC/9 mast cells, M1 leukemia cells, U3A human fibroblasts, and primary mouse CD4+ T cells. Induction of SOCS molecules is dependent on STAT3 activation by IL-10R1. Cell lines constitutively overexpressing SOCS proteins demonstrated that SOCS1 and SOCS3, but not SOCS2, are able to partially inhibit IL-10-mediated STAT3 activation and proliferative responses. Pretreatment of M1 cells with IFN-γ resulted in SOCS1 induction and a reduction of IL-10-mediated STAT3 activation and cell growth inhibition. IL-10-induced SOCS is associated with the inhibition of IFN-γ signaling in various cell types, and this inhibition is independent of C-terminal serine residues of the IL-10R, previously shown to be required for other anti-inflammatory responses. Thus, the present results show that both SOCS1 and SOCS3 are induced by IL-10 and may be important inhibitors of both IL-10 and IFN-γ signaling. IL-10-induced SOCS1 may directly inhibit IL-10 IFN-γ signaling, while inhibition of other proinflammatory cytokine responses may use additional IL-10R1-mediated mechanisms.Keywords
This publication has 34 references indexed in Scilit:
- Heme oxygenase-1 mediates the anti-inflammatory effect of interleukin-10 in miceNature Medicine, 2002
- IL‐10 attenuates IFN‐α‐activated STAT1 in the liver: involvement of SOCS2 and SOCS3FEBS Letters, 2000
- Stat3-Mediated Transformation of NIH-3T3 Cells by the Constitutively Active Q205L Gα o ProteinScience, 2000
- SOCS1 Is a Critical Inhibitor of Interferon γ Signaling and Prevents the Potentially Fatal Neonatal Actions of this CytokineCell, 1999
- Interleukin-10 Receptor Signaling through the JAK-STAT PathwayPublished by Elsevier BV ,1999
- CIS3 and JAB have different regulatory roles in interleukin-6 mediated differentiation and STAT3 activation in M1 leukemia cellsOncogene, 1998
- Regulation of contact hypersensitivity by interleukin 10.The Journal of Experimental Medicine, 1994
- Interleukin‐4 and interleukin‐10 synergize to inhibit cell‐mediated immunity in vivoEuropean Journal of Immunology, 1993
- Macrophage deactivation by interleukin 10.The Journal of Experimental Medicine, 1991
- Interleukin 10(IL-10) inhibits cytokine synthesis by human monocytes: an autoregulatory role of IL-10 produced by monocytes.The Journal of Experimental Medicine, 1991