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Cited by 167

The DOI matches its Crossref record; 13 of the 13 references it cites were found in a registry or an index.

Molecular Mechanism of Lipopolysaccharide-Induced SOCS-3 Gene Expression in Macrophages and Microglia

Open access
Qin, Hongwei, Roberts, Kevin L, Niyongere, Sandrine A, Cong, Yingzi, Elson, Charles O, Benveniste, Etty N·2007·The Journal of Immunology

Abstract

Immunological activation of macrophages/microglia within the CNS leads to the production of cytokines and chemokines that ultimately impact on glial and neuronal function. Suppressor of cytokine signaling (SOCS) proteins are negative regulators of adaptive and innate immune responses. Our previous studies demonstrated that SOCS-3 attenuates macrophage/microglial activation in vitro, suggesting that SOCS-3 may exert beneficial effects for immune-mediated CNS diseases in vivo. In this study, we describe LPS as a potent inducer of SOCS-3 transcription and expression in macrophages/microglia. An analysis of the SOCS-3 promoter indicates that AP-1 and IFN-γ activation sequence (GAS) elements are involved in LPS-induced SOCS-3 transcription. LPS-induced SOCS-3 expression was diminished in IL-10-deficient macrophages at later time points, indicating the involvement of endogenous IL-10 in this response. Blocking STAT-3 expression and activation using STAT-3 small interfering RNA reduced LPS-induced SOCS-3 gene expression. LPS activated the MAPK-ERK1/2, JNK, and p38 pathways that, in addition to STAT-3, were also involved in LPS-induced SOCS-3 expression. LPS treatment of cells led to the acetylation of histones H3 and H4 on the SOCS-3 promoter and the recruitment of STAT-3, c-Jun, c-Fos, CREB-binding protein, p300, and RNA polymerase II to the endogenous SOCS-3 promoter in a time-dependent manner. These results indicate that LPS-induced MAPK activation, the production of endogenous IL-10, and STAT-3 activation play critical roles in SOCS-3 expression, which provides for feedback attenuation of cytokine-induced immune and inflammatory responses in macrophages and microglia.

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Metadata

Authors
Qin, H., Roberts, K. L., Niyongere, S. A., Cong, Y., Elson, C. O., & Benveniste, E. N.
Venue
The Journal of Immunology
Published
2007-11-01
Volume
179
Issue
9
Pages
5966-5976
ISSN
  • 0022-1767 (ISSN-L)
  • 1550-6606
OpenAlex
W2105564248
Cited by
167
References
13
FWCI
5.28
Type
journal article
Language
en
Open access
bronze

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CoChat. (2026). Citation check: Molecular Mechanism of Lipopolysaccharide-Induced SOCS-3 Gene Expression in Macrophages and Microglia. https://app.cochat.ai/papers/10.4049/jimmunol.179.9.5966
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Qin, H., Roberts, K. L., Niyongere, S. A., Cong, Y., Elson, C. O., & Benveniste, E. N. (2007). Molecular Mechanism of Lipopolysaccharide-Induced SOCS-3 Gene Expression in Macrophages and Microglia. The Journal of Immunology. https://doi.org/10.4049/jimmunol.179.9.5966

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