Differential Production of and Migratory Response to   Chemokines by Human Microglia and Astrocytes

Peterson, Phillip K.; Hu, Shuxian; Salak‐Johnson, Janeen L.; Molitor, Thomas W.; Chao, Chun C.

doi:10.1093/infdis/175.2.478

Cited by 192 publications

(131 citation statements)

References 10 publications

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“…This is consistent with our data, where all the chemokines induced (MIP-1␣, MIP-1␤, MCP-1, IP-10, and RANTES) have been implicated in the chemotaxis of macrophages (56,57) and microglia (50,51,53), the predominant cell types recruited into the demyelinating lesion during cuprizone treatment (23). MIP-2, lymphotactin, eotaxin, and TCA-3 were not observed (Fig.…”

Section: Discussionsupporting

confidence: 93%

Absence of Macrophage-Inflammatory Protein-1α Delays Central Nervous System Demyelination in the Presence of an Intact Blood-Brain Barrier

McMahon

Cook

Suzuki

et al. 2001

The Journal of Immunology

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Chemokines are small chemotactic cytokines that modulate leukocyte recruitment and activation during inflammation. Here, we describe the role of macrophage inflammatory protein-1α (MIP-1α) during cuprizone intoxication, a model where demyelination of the CNS features a large accumulation of microglia/macrophage without T cell involvement or blood-brain barrier disruption. RNase protection assays showed that mRNA for numerous chemokines were up-regulated during cuprizone treatment in wild-type, C57BL/6 mice. RANTES, inflammatory protein-10, and monocyte chemoattractant protein-1 showed greatest expression with initiation of insult at 1–2 wk of treatment, whereas MIP-1α and β increased later at 4–5 wk, coincident with peak demyelination and cellular accumulation. The function of MIP-1α during demyelination was tested in vivo by exposing MIP-1α knockout mice (MIP-1α−/−) to cuprizone and comparing pathology to wild-type mice. Demyelination at 3.5 wk of treatment was significantly decreased in MIP-1α−/− mice (∼36% reduction), a result confirmed by morphology at the electron microscopic level. The delay in demyelination was correlated to apparent decreases in microglia/macrophage and astrocyte accumulation and in TNF-α protein levels. It was possible that larger effects of the MIP-1α deficiency were being masked by other redundant chemokines. Indeed, RNase protection assays revealed increased expression of several chemokine transcripts in both untreated and cuprizone-treated MIP-1α−/− mice. Nonetheless, despite this possible compensation, our studies show the importance of MIP-1α in demyelination in the CNS and highlight its effect, particularly on cellular recruitment and cytokine regulation.

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Section: Discussionsupporting

confidence: 93%

Absence of Macrophage-Inflammatory Protein-1α Delays Central Nervous System Demyelination in the Presence of an Intact Blood-Brain Barrier

McMahon

Cook

Suzuki

et al. 2001

The Journal of Immunology

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“…A subpopulation of astroglia express functional MOR (Eriksson et al, 1991;Stiene-Martin and Hauser, 1991;Hauser et al, 1996;Stiene-Martin et al, 1998;Stiene-Martin et al, 2001) and opiates markedly increase the production of chemokines by HIV-1 Tat exposed astrocytes . Astrocytes are an important source of chemokines in the CNS and express CCL2 (Ransohoff et al, 1993;Hayashi et al, 1995;Peterson et al, 1997;Oh et al, 1999) and variably express its cognate receptor CCR2 (Andjelkovic et al, 1999;Dorf et al, 2000), although CCR2 expression among astrocytes is heterogeneous and appears to be regulated by inflammation (Andjelkovic et al, 2002;Croitoru-Lamoury et al, 2003). HIV-1 Tat triggers CCL2 production and inflammatory cascades in astrocytes (Conant et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

CCR2 mediates increases in glial activation caused by exposure to HIV-1 Tat and opiates

El‐Hage

Ambati

et al. 2006

Journal of Neuroimmunology

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To assess the role of CCL2/MCP-1 in opiate drug abuse and HIV-1 comorbidity, the effects of systemic morphine and intrastriatal HIV-1 Tat on macrophage/microglial and astroglial activation were assessed in wild type and CCR2 null mice. Tat and/or morphine additively increased the proportion of CCL2 immunoreactive astroglia. The effects of morphine were prevented by naltrexone. Glial activation was significantly reduced in CCR2(−/−) versus wild-type mice following Tat or morphine plus Tat exposure. Thus, CCR2 contributes to local glial activation caused by Tat alone or in the presence of opiates, implicating CCR2 signaling in HIV-1 neuropathogenesis in drug abusers and non-abusers.

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“…Anti-MIP-1a antibodies prevented the development of EAE [17]. Astrocyte-derived chemokines within the CNS were able to participate in the recruitment of peripheral blood monocytes or T lymphocytes in autoimmune [17,18] or infectious diseases [19] as well as in acute trauma of the CNS [18].…”

Section: Introductionmentioning

confidence: 99%

“…Bacterial lipopolysaccharide (LPS), tumour necrosis factor-a (TNF-a), interferon-g (IFN-g) and interleukin-1b (IL-1b) have been shown to trigger astrocytes to up-regulate chemokine expression in vitro [18,20]. However, the majority of these investigations were performed on human fetal astrocytes or newborn rat/mouse astrocytes and therefore little is known about the expression and regulation of chemokines in adult rat astrocytes.…”

Section: Introductionmentioning

confidence: 99%

Regulation of β‐Chemokine mRNA Expression in Adult Rat Astrocytes by Lipopolysaccharide, Proinflammatory and Immunoregulatory Cytokines

et al. 1998

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Regulation of b-Chemokine mRNA Expression in Adult Rat Astrocytes by Lipopolysaccharide, Proinflammatory and Immunoregulatory Cytokines. Scand J Immunol 1998;48:502-508 Astrocytes constitute a part of the blood-brain barrier. Chemokine expression by astrocytes may contribute to leucocyte infiltration within the central nervous system (CNS) during inflammation. To investigate factor(s) regulating chemokine expression by astrocytes, we studied the induction of b-chemokine mRNA expression in adult rat astrocytes. Astrocyte-derived monocyte chemoattractant protein-1 (MCP-1), RANTES, macrophage inflammatory protein (MIP)-1a and MIP-1b mRNA were induced by interferon-g (IFN-g). Tumour necrosis factor-a (TNF-a) induced MCP-1, RANTES and MIP-1b mRNA expression, and lipopolysaccharide (LPS) induced MCP-1, MIP-1a and MIP-1b mRNA expression in astrocytes. LPS-induced MCP-1, MIP-1a and MIP-1b mRNA expression by astrocytes was antagonized by transforming growth factor (TGF)-b1 and interleukin (IL)-10. TGF-b1 and IL-10 also down-regulated MCP-1 and RANTES mRNA expression induced by TNF-a. IL-10, but not TGF-b1, inhibited MIP-1b mRNA expression induced by TNF-a. The results of this in vitro study suggest that b-chemokine mRNA expression by adult rat astrocytes can be induced by LPS or proinflammatory cytokines, while regulatory cytokines, such as TGF-b1 and IL-10, down-regulate astrocytederived b-family chemokine mRNA expression induced by LPS, IFN-g and TNF-a. Further study of CNS chemokines will enhance our understanding of leucocyte recruitment to the CNS and suggest therapeutic strategies for neurological disorders.

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Differential Production of and Migratory Response to Chemokines by Human Microglia and Astrocytes

Cited by 192 publications

References 10 publications

Absence of Macrophage-Inflammatory Protein-1α Delays Central Nervous System Demyelination in the Presence of an Intact Blood-Brain Barrier

Absence of Macrophage-Inflammatory Protein-1α Delays Central Nervous System Demyelination in the Presence of an Intact Blood-Brain Barrier

CCR2 mediates increases in glial activation caused by exposure to HIV-1 Tat and opiates

Regulation of β‐Chemokine mRNA Expression in Adult Rat Astrocytes by Lipopolysaccharide, Proinflammatory and Immunoregulatory Cytokines

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