Distinct patterns of stimulus-inducible chemokine mRNA accumulation in human fetal astrocytes and microglia

Hua, Liwei L.; Lee, Sunhee C.

doi:10.1002/(sici)1098-1136(200003)30:1<74::aid-glia8>3.0.co;2-c

Cited by 94 publications

(58 citation statements)

References 47 publications

(33 reference statements)

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“…That both fetal and adult human astrocytes can be activated by IL-1␤ to express IL-8 and IP-10 has been well established (Oh et al, 1999;Hua and Lee, 2000). IL-8 is an ELR-positive (i.e., Glu-Leu-Arg motif-containing) ␣ chemokine that is principally recognized for its role as a chemotactic factor for neutrophils (Yasumoto et al, 1992), and levels of IL-8 rise dramatically in the CSF of patients with bacterial meningitis (Spanaus et al, 1997), as well as after brain injury, ischemia, and stroke (Tarkowski et al, 1997;Whalen et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

“…Previous work has shown that in human fetal astrocytes, IL-1␤ induces expression of chemokines including IL-8, IP-10, and monocyte chemotactic protein-1 (Oh et al, 1999;Hua and Lee, 2000). To determine whether the effects of ATP on IL-1␤-induced transcription factor activation were associated with changes in IL-1␤-induced inflammatory gene expression, astrocytes were treated with IL-1␤, ATP, or both, and chemokine mRNA and protein were analyzed using RNase protection assay and sandwich ELISA.…”

Section: Extracellular Atp Differentially Regulates Il-1␤-induced Expmentioning

confidence: 99%

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Extracellular Nucleotides Differentially Regulate Interleukin-1β Signaling in Primary Human Astrocytes: Implications for Inflammatory Gene Expression

John¹,

Simpson

Woodroofe

et al. 2001

J. Neurosci.

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The cytokine interleukin-1␤ (IL-1␤) is a potent activator of human astrocytes, inducing or modulating expression of multiple proinflammatory genes via activation of the transcription factors nuclear factor-B (NF-B) and activator protein-1 (AP-1). In this study, we examined whether IL-1␤ signaling is regulated in these cells by extracellular nucleotides that are released at high concentrations under inflammatory conditions and act as ligands for members of the P2 receptor family. Using reporter constructs and electromobility shift assays, we found that cotreatment of astrocyte cultures with ATP (1-100 M) significantly potentiated IL-1␤-mediated activation of NF-B and AP-1 and that ATP alone activated AP-1. These effects were blocked by the P2 receptor antagonists XAMR 0721, periodate-oxidized ATP, and suramin. A role for ATP in modulating IL-1␤-mediated inflammatory gene expression was supported further by the observation that ATP potentiated the IL-1␤-induced expression of IL-8 mRNA and protein but strongly downregulated IP-10 expression. Reverse transcription-PCR and cloning demonstrated expression of the ATP-responsive P2 receptor subtypes P2Y 1 , P2Y 2 , and P2X 7 , as well as the ATP-insensitive receptor P2Y 4 . ADP, a selective agonist for P2Y 1 , produced results similar to or greater than those obtained using ATP, whereas 2Ј-3Ј-O-(4-benzoylbenzoyl)-ATP, a selective agonist for P2X 7 , was less effective than ATP. In contrast, UTP, a selective agonist for P2Y 2 and P2Y 4 , was ineffective. These studies indicate that different P2 receptor subtypes play distinct roles in the modulation of IL-1␤-mediated signal transduction in human astrocytes, and that signaling via P2 receptors may fine-tune the transcription of genes involved in inflammatory responses in the human CNS.

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Section: Discussionmentioning

confidence: 99%

Section: Extracellular Atp Differentially Regulates Il-1␤-induced Expmentioning

confidence: 99%

Extracellular Nucleotides Differentially Regulate Interleukin-1β Signaling in Primary Human Astrocytes: Implications for Inflammatory Gene Expression

John¹,

Simpson

Woodroofe

et al. 2001

J. Neurosci.

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“…29 Previous investigations of human fetal microglia, however, found no significant production of the CCL4/MIP-1b mRNA or protein by IFN-g activation. 15,16,24 This contradictory finding may simply reflect the greater sensitivity of microarray analysis for assessing gene expression than other techniques, or that the enhanced gene expression does not result in a corresponding increase in protein expression. RT-PCR confirmed.…”

Section: Data Summarymentioning

confidence: 99%

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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“…Besides IFN-␣/␤, and IFN-␥, proinflammatory cytokines, such as TNF-␣ and IL-1␤, also have been shown to be capable of inducing astrocytic IP-10 gene expression, although with a lower efficiency (43). Triple knockout mice still possess functional NK cells, which are a possible source of proinflammatory cytokines (15).…”

Section: Vol 74 2000 Bdv and Chemokine Gene Expression In Astrocytementioning

confidence: 99%

Chemokine Gene Expression in Astrocytes of Borna Disease Virus-Infected Rats and Mice in the Absence of Inflammation

Sauder

Hallensleben

Pagenstecher

et al. 2000

J Virol

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Borna disease virus (BDV) causes CD8؉ T-cell-mediated meningoencephalitis in immunocompetent mice and rats, thus providing a valuable animal model for studying the mechanisms of virus-induced central nervous system (CNS) immunopathology. Chemokine-mediated leukocyte recruitment to the CNS is a crucial step in the development of neurological disease. We found increased mRNA levels of IP-10 and other chemokines in brains of adult rats following infection with BDV. The marked increase in chemokine gene expression at about day 8 postinfection seemed to immediately precede the inflammatory process. In brains of rats infected as newborns, in which inflammation was only mild and transient, sustained expression of IP-10 and RANTES genes was observed. In situ hybridization studies revealed that astrocytes were the major source of IP-10 mRNAs in brains of rats infected as newborns and as adults. In brains of infected mice lacking CD8 ؉ T cells (␤2m 0/0 ), transcripts encoding IP-10 and RANTES were also observed. IP-10 transcripts were also present in a small number of scattered astrocytes of infected knockout mice lacking mature B and T cells as well as functional alpha/beta and gamma interferon receptors, indicating that BDV can induce chemokine synthesis in the absence of interferons and other B-or T-cell-derived cytokines. These data provide strong evidence that CNS-resident cells are involved in the early localized host immune response to infection with BDV and support the concept that chemokines are pivotal for the initiation of virus-induced CNS inflammation.

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Distinct patterns of stimulus-inducible chemokine mRNA accumulation in human fetal astrocytes and microglia

Cited by 94 publications

References 47 publications

Extracellular Nucleotides Differentially Regulate Interleukin-1β Signaling in Primary Human Astrocytes: Implications for Inflammatory Gene Expression

Extracellular Nucleotides Differentially Regulate Interleukin-1β Signaling in Primary Human Astrocytes: Implications for Inflammatory Gene Expression

Transcriptional response of human microglial cells to interferon-γ

Chemokine Gene Expression in Astrocytes of Borna Disease Virus-Infected Rats and Mice in the Absence of Inflammation

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