Chemokine-enhanced migration of human peripheral blood mononuclear cells is antagonized by interferon beta-1b through an effect on matrix metalloproteinase-9

Stüve, Olaf; Chabot, Sophie; Jung, Sonia S.; Williams, Gary J.; Yong, V. Wee

doi:10.1016/s0165-5728(97)00134-3

Cited by 99 publications

(57 citation statements)

References 63 publications

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“…In the CNS, both astrocytes and microglia express MMP9 (28), and it is also expressed by infiltrating macrophages (44). It has been shown that type I IFN inhibits MMP9 expression in astrocytes and microglia and reduces leukocyte infiltration to the CNS (29,43,(45)(46)(47). We find that in the absence of type I IFN signaling, MMP9 was significantly increased.…”

Section: Discussionmentioning

confidence: 64%

“…Our findings further suggest that type I IFN signaling may regulate leukocyte entry through this or other mechanisms involving disruption of blood-brain barrier (29). MMP9 is involved in degradation of extracellular matrix and facilitating the recruitment of leukocytes (28,43). In the CNS, both astrocytes and microglia express MMP9 (28), and it is also expressed by infiltrating macrophages (44).…”

Section: Discussionmentioning

confidence: 72%

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Injury-Induced Type I IFN Signaling Regulates Inflammatory Responses in the Central Nervous System

Khorooshi

Owens

2010

The Journal of Immunology

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Innate glial response is critical for the induction of inflammatory mediators and recruitment of leukocytes to sites of the injury in the CNS. We have examined the involvement of type I IFN signaling in the mouse hippocampus following sterile injury (transection of entorhinal afferents). Type I IFNs signal through a receptor (IFNAR), which involves activation of IFN regulatory factor (IRF)9, leading to the induction of IFN-stimulated genes including IRF7, that in turn enhances the induction of type I IFN. Axonal transection induced upregulation of IRF7 and IRF9 in hippocampus. Induction of IRF7 and IRF9 mRNAs was IFNAR dependent. Double-labeling immunofluorescence showed that IRF7 selectively was induced in Mac-1/CD11b+ macrophages/microglia in hippocampus after axonal transection. IRF7 mRNA was also detected in microglia sorted by flow cytometry. Lack of type I IFN signaling resulted in increased leukocyte infiltration into the lesion-reactive hippocampus. Axonal lesion-induced CXCL10 gene expression was abrogated, whereas matrix metalloproteinase 9 mRNA was elevated in IFNAR-deficient mice. Our findings point to a role for type I IFN signaling in regulation of CNS response to sterile injury.

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Section: Discussionmentioning

confidence: 64%

Section: Discussionmentioning

confidence: 72%

Injury-Induced Type I IFN Signaling Regulates Inflammatory Responses in the Central Nervous System

Khorooshi

Owens

2010

The Journal of Immunology

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“…Together these data suggest that endogenous IFN-␤ does not affect the primary activation of encephalitogenic T cells in peripheral lymphoid organs and hence does not influence the initiation phase of the disease. Nevertheless, one could assume that IFN-␤ can influence T cell effector functions after the initial activation, as it has been reported that IFN-␤ inhibits matrix metalloproteinase-9 in T cells cultured in vitro (15,16) and down-regulates very late Ag-4 (VLA-4) on lymphocytes from MS patients (27), and this could impair T cell ability to cross the BBB (28,29). Our observation of activation-induced down-regulation of VCAM-1 observed on the in vitro cultured macrophages could be important for cell adhesion and migration.…”

Section: Discussionmentioning

confidence: 99%

IFN-β Gene Deletion Leads to Augmented and Chronic Demyelinating Experimental Autoimmune Encephalomyelitis

Teige

Treschow

Teige

et al. 2003

The Journal of Immunology

191

190

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Since the basic mechanisms behind the beneficial effects of IFN-β in multiple sclerosis (MS) patients are still obscure, here we have investigated the effects of IFN-β gene disruption on the commonly used animal model for MS, experimental autoimmune encephalomyelitis (EAE). We show that IFN-β knockout (KO) mice are more susceptible to EAE than their wild-type (wt) littermates; they develop more severe and chronic neurological symptoms with more extensive CNS inflammation and demyelination. However, there was no discrepancy observed between wt and KO mice regarding the capacity of T cells to proliferate or produce IFN-γ in response to recall Ag. Consequently, we addressed the effect of IFN-β on encephalitogenic T cell development and the disease initiation phase by passive transfer of autoreactive T cells from KO or wt littermates to both groups of mice. Interestingly, IFN-β KO mice acquired a higher incidence and augmented EAE regardless of the source of T cells. This shows that the anti-inflammatory effect of endogenous IFN-β is predominantly exerted on the effector phase of the disease. Histopathological investigations of CNS in the effector phase revealed an extensive microglia activation and TNF-α production in IFN-β KO mice; this was virtually absent in wt littermates. This coincided with an increase in effector functions of T cells in IFN-β KO mice, as measured by IFN-γ and IL-4 production. We suggest that lack of endogenous IFN-β in CNS leads to augmented microglia activation, resulting in a sustained inflammation, cytokine production, and tissue damage with consequent chronic neurological deficits.

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“…25 Blood vessels and mononuclear cells present inside the blood vessels displayed immunoreactivity for MMP-9 in these active lesions. Stüve et al 26 found that chemokines enhanced the production of MMP-9 by peripheral blood cells and that IFN-␤1b reduced this MMP-9 production. This is partly accountable for the beneficial effect of IFN-␤1b in the treatment of MS patients.…”

Section: Discussionmentioning

confidence: 99%

Expression of MCP-1 by Reactive Astrocytes in Demyelinating Multiple Sclerosis Lesions

Voorn

Tekstra

Beelen

et al. 1999

The American Journal of Pathology

237

141

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The pathology of multiple sclerosis (MS) is characterized by breakdown of the blood-brain barrier (BBB), accompanied by infiltration of macrophages and T lymphocytes into the central nervous system (CNSMultiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system (CNS), characterized by neurological symptoms caused by impaired nerve conduction. Clinical signs of MS are a result of inflammatory lesions in the CNS. Early in lesion development there is breakdown of the blood-brain barrier (BBB), allowing mononuclear cells to enter the CNS. These cells form perivascular cell infiltrates (cuffs) and migrate into the parenchyma of the brain. The monocytes become activated to parenchymal macrophages, which engulf and degrade myelin, and oligodendrocyte death occurs.

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Chemokine-enhanced migration of human peripheral blood mononuclear cells is antagonized by interferon beta-1b through an effect on matrix metalloproteinase-9

Cited by 99 publications

References 63 publications

Injury-Induced Type I IFN Signaling Regulates Inflammatory Responses in the Central Nervous System

Injury-Induced Type I IFN Signaling Regulates Inflammatory Responses in the Central Nervous System

IFN-β Gene Deletion Leads to Augmented and Chronic Demyelinating Experimental Autoimmune Encephalomyelitis

Expression of MCP-1 by Reactive Astrocytes in Demyelinating Multiple Sclerosis Lesions

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