Inhibition of microglial cell RANTES production by IL-10 and TGF-β

Hu, Shuxian; Chao, Chun C.; Ehrlich, Laura; Sheng, Wen S.; Sutton, Richard L.; Rockswold, Gaylan L.; Peterson, Phillip K.

doi:10.1002/jlb.65.6.815

Cited by 97 publications

(83 citation statements)

References 31 publications

(53 reference statements)

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“…It remains to be established whether, in the latter two studies, IL-10 inhibited production of IL-1 as it does in macrophages (24) or whether it antagonizes the effect of IL-1. In this context, it is significant that IL-10 (at the same concentration used in the present study) has been shown to inhibit the IL-1␤-induced increase in IL-6 production in astrocytes (53) and RANTES (regulated on activation normal T cell expressed and secreted) mRNA expression in microglia (54).…”

Section: Il-10 Antagonizes Il-1␤ Effect In Hippocampusmentioning

confidence: 57%

The Anti-inflammatory Cytokine, Interleukin (IL)-10, Blocks the Inhibitory Effect of IL-1β on Long Term Potentiation

Kelly

Lynch

Vereker

et al. 2001

Journal of Biological Chemistry

127

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Several effects of the proinflammatory cytokine, interleukin-1␤ (IL-1␤), have been described in the central nervous system, and one area of the brain where marked changes have been reported is the hippocampus. Among these changes are an IL-1␤-induced inhibition of long term potentiation (LTP) in perforant path-granule cell synapses and an attenuation of glutamate release in synaptosomes prepared from the hippocampus. Evidence suggests that, at least in circulating cells, the anti-inflammatory cytokine, IL-10, antagonizes certain effects of IL-1. We investigated the effect of IL-10 on IL-1␤-induced inhibition of LTP and glutamate release. The evidence presented indicates that IL-1␤ stimulates the stress-activated protein kinase, c-Jun-activated protein kinase (JNK), and IL-1 receptor-associated kinase, which may explain its inhibitory effect on release and LTP, and that IL-10 reversed the IL-1␤-induced stimulation of JNK activity and inhibition of release and LTP. We observed that IL-10 abrogated the stimulatory effect of IL-1␤ on superoxide dismutase activity and reactive oxygen species production, whereas the H 2 O 2 -induced inhibition of LTP was also blocked by IL-10. We present evidence that suggests that the action of IL-10 may be mediated by its ability to induce shedding of the IL-1 type I receptor.

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Section: Il-10 Antagonizes Il-1␤ Effect In Hippocampusmentioning

confidence: 57%

The Anti-inflammatory Cytokine, Interleukin (IL)-10, Blocks the Inhibitory Effect of IL-1β on Long Term Potentiation

Kelly

Lynch

Vereker

et al. 2001

Journal of Biological Chemistry

127

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“…Anti-inflammatory cytokines are important regulators of potentially damaging inflammatory responses within the CNS. Previous work in our laboratory has demonstrated that anti-inflammatory cytokines such as IL-10, IL-4, and TGF-␤ inhibit chemokine production from stimulated microglial cells (15,21). We next assessed the effects of IL-10, IL-4, and TGF-␤ on CMV-induced CXCL10 expression.…”

Section: Resultsmentioning

confidence: 99%

“…The immunosuppressive microenvironment of the CNS (23), as well as the upregulation of anti-inflammatory cytokines during various insults within the brain, appears to be required to maintain or restore homeostasis to this vital organ (67). It has been postulated that the anti-inflammatory microenvironment of the brain is maintained through constitutive expression of low levels of TGF-␤, while other anti-inflammatory cytokines, such as IL-10 and IL-4, execute a more acute quenching of inflammatory processes (21). These anti-inflammatory cytokines are known to suppress chemokine production by activated microglial cells through a unique directed regulation of specific inflammatory processes rather than global suppression of cellular function (15,19,21,59).…”

Section: Discussionmentioning

confidence: 99%

“…Anti-inflammatory cytokines like interleukin-10 (IL-10), IL-4, and transforming growth factor ␤ (TGF-␤) are also produced during viral CNS infection (69). These cytokines have been demonstrated to inhibit the production of proinflammatory factors, thereby counteracting potentially deleterious consequences of the inflammatory response (15,21,45,52). Viruses have also evolved homologues to these anti-inflammatory cytokines, possibly as a mechanism by which to evade host immune responses.…”

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confidence: 99%

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CXCL10 Production from Cytomegalovirus-Stimulated Microglia Is Regulated by both Human and Viral Interleukin-10

Cheeran

Sheng

et al. 2003

J Virol

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Glial cells orchestrate immunocyte recruitment to focal areas of viral infection within the brain and synchronize immune cell functions through a regulated network of cytokines and chemokines. Since recruitment of T lymphocytes plays a critical role in resolving cytomegalovirus (CMV) infection, we investigated the production of a T-cell chemoattractant, CXCL10 (gamma interferon-inducible protein 10) in response to viral infection of human glial cells. Infection with CMV was found to elicit the production of CXCL10 from primary microglial cells but not from astrocytes. This CXCL10 expression was not dependent on secondary protein synthesis but did require the phosphorylation of p38 mitogen-activated protein (MAP) kinase. In addition, migration of activated lymphocytes toward supernatants from CMV-stimulated microglial cells was partially suppressed by anti-CXCL10 antibodies. Since regulation of central nervous system inflammation is essential to allow viral clearance without immunopathology, microglial cells were then treated with anti-inflammatory cytokines. CMV-induced CXCL10 production from microglial cells was suppressed following treatment with interleukin-10 (IL-10) and IL-4 but not following treatment with transforming growth factor ␤. The IL-10-mediated inhibition of CXCL10 production was associated with decreased CMV-induced NF-B activation but not decreased p38 MAP kinase phosphorylation. Finally, CMV infection of fully permissive astrocytes resulted in mRNA expression for the viral homologue to human IL-10 (i.e., cmvIL-10 [UL111a]) in its spliced form and conditioned medium from CMV-infected astrocytes inhibited virus-induced CXCL10 production from microglial cells through the IL-10 receptor. These findings present yet another mechanism through which CMV may subvert host immune responses.

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“…Human microglia synthesize CCL5/RANTES in response to proinflammatory stimuli, such as IL-1b and TNF-a, and the anti-inflammatory cytokines IL-10 and TGF-b downregulate its production. 26 Previous studies on human fetal microglia and monocyte-derived macrophages, however, have not demonstrated an increased CCL5/RANTES production in response to IFN-g. 15,16 While the reasons for this discrepancy are not clear, the results show an increased expression of CCL5/ RANTES at both the mRNA and protein level, confirming that there is a significant increase in the expression of this mediator in response to IFN-g stimulation in microglial cells.…”

Section: Data Summarymentioning

confidence: 93%

Transcriptional response of human microglial cells to interferon-γ

Rock

Deshpande

et al. 2005

Genes Immun

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Microglia, the resident macrophages in the central nervous system (CNS), play a pivotal role in innate and adaptive immune responses in the brain. The immune functions of microglia are regulated by cytokines, including interferon (IFN)-g, which is a major mediator of macrophage activation. We describe the transcriptional profile of human fetal microglial cells at 1, 6, and 24 h after IFN-g treatment. The results show a change in the expression of 405 genes including transcriptionally induced chemokines, IFN-g signaling factors, and major histocompatibility complex genes. Our results demonstrate that activation of microglia by IFN-g induces proinflammatory T-lymphocyte-related chemokine genes as well as genes involved in antigen presentation. As a result, signals for T-cell infiltration and antigen presentation are produced to allow for microglia-T-cell interactions that likely contribute to defense against invading pathogens. In sum, our results provide a foundation for the molecular mechanisms of the microglial response to IFN-g-a key to understanding cell-mediated immunity of the CNS.

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Inhibition of microglial cell RANTES production by IL-10 and TGF-β

Cited by 97 publications

References 31 publications

The Anti-inflammatory Cytokine, Interleukin (IL)-10, Blocks the Inhibitory Effect of IL-1β on Long Term Potentiation

The Anti-inflammatory Cytokine, Interleukin (IL)-10, Blocks the Inhibitory Effect of IL-1β on Long Term Potentiation

CXCL10 Production from Cytomegalovirus-Stimulated Microglia Is Regulated by both Human and Viral Interleukin-10

Transcriptional response of human microglial cells to interferon-γ

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