Acute and relapsing experimental autoimmune encephalomyelitis are regulated by differential expression of the CC chemokines macrophage inflammatory protein-1α and monocyte chemotactic protein-1

Kennedy, Kevin J.; Strieter, Robert M.; Kunkel, Steven L.; Lukacs, Nicholas W.; Karpus, William J.

doi:10.1016/s0165-5728(98)00187-8

Cited by 228 publications

(187 citation statements)

References 39 publications

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“…MOG-induced EAE in mice is recognized to be a good experimental model of human MS pathogenesis [7,36,37], and in the present study MOG ( The observed effect could not be due to inhibition of bone marrow cell mobilization, as has been reported for inhibitors of the GPC receptor CCR2 [38,39], since we have already…”

Section: Discussionsupporting

confidence: 73%

Interfering with the CCL2–glycosaminoglycan axis as a potential approach to modulate neuroinflammation

Gschwandtner

Piccinini

Gerlza

et al. 2016

Neuroscience Letters

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Section: Discussionsupporting

confidence: 73%

Interfering with the CCL2–glycosaminoglycan axis as a potential approach to modulate neuroinflammation

Gschwandtner

Piccinini

Gerlza

et al. 2016

Neuroscience Letters

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“…Thus, treatment with anti-MIP-1␣, but not anti-MCP-1, inhibited acute EAE. Conversely, anti-MCP-1 moderately reduced relapsing EAE severity, whereas anti-MIP-1␣ had no effect at this stage of the disease (16). In MBP/CFA-immunized SJL mice, we show that the protective effect of G-CSF correlated with a reduced MIP-1␣/MCP-1 production ratio in the autoreactive response at both mRNA and protein levels.…”

Section: Discussionmentioning

confidence: 63%

“…More recently, therapeutic strategies have been aimed at the neutralization of chemokines, based on reports showing that expression of chemokines, particularly the CC chemokine macrophage inflammatory protein-1␣ (MIP-1␣), and chemokine receptors in the CNS correlated with EAE disease symptoms (13) and was increased in patients with acute MS (14,15). Treatments of proteolipid protein-or myelin basic protein (MBP)-immunized SJL/J mice with anti-MIP-1␣ was able to inhibit acute EAE severity (16). Of particular relevance to the role of chemokines in autoimmune settings is the fact that in addition to driving leukocyte attraction and accumulation to tissue sites of inflammation, chemokines play a regulatory role in T cell proliferation, differentiation, and Th1/Th2 balance in cytokine production (17)(18)(19).…”

mentioning

confidence: 99%

G-CSF Therapy of Ongoing Experimental Allergic Encephalomyelitis Via Chemokine- and Cytokine-Based Immune Deviation

Zavala

Abad

Ezine

et al. 2002

The Journal of Immunology

108

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Converging evidence that G-CSF, the hemopoietic growth factor of the myeloid lineage, also exerts anti-inflammatory and pro-Th2 effects, prompted us to evaluate its direct therapeutic potential in autoimmune diseases. Here we report a novel activity of G-CSF in experimental allergic encephalomyelitis, a murine model for multiple sclerosis, driven by Th1-oriented autoaggressive cells. A short 7-day treatment with G-CSF, initiated at the onset of clinical signs, provided durable protection from experimental autoimmune encephalomyelitis. G-CSF-treated mice displayed limited demyelination, reduced recruitment of T cells to the CNS, and very discrete autoimmune inflammation, as well as barely detectable CNS mRNA levels of cytokines and chemokines. In the periphery, G-CSF treatment triggered an imbalance in the production by macrophages as well as autoreactive splenocytes of macrophage inflammatory protein-1α and monocyte chemoattractant protein-1, the prototypical pro-Th1 and pro-Th2 CC chemokines, respectively. This chemokine imbalance was associated with an immune deviation of the autoreactive response, with reduced IFN-γ and increased IL-4 and TGF-β1 levels. Moreover, G-CSF limited the production of TNF-α, a cytokine also associated with early CNS infiltration and neurological deficit. These findings support the potential application of G-CSF in the treatment of human autoimmune diseases such as multiple sclerosis, taking advantage of the wide clinical favorable experience with this molecule.

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“…Hybridoma cell lines producing mAb against mouse CCL5 were created by immunizing BALB/c mice with a peptide corresponding to an epitope (KKWVQEYINYLEMS) previously shown to produce neutralizing Abs to CCL5 (17,28,29). Spleens from immunized mice were removed and fused with SP2/0 myeloma cells using polyethylene glycol (30).…”

Section: Anti-ccl5 Mabmentioning

confidence: 99%

“…R6G9 showed reactivity to recombinant mouse CCL5 (rCCL5; Cell Sciences, Norwood, MA) to a dilution of 1/156,000 via ELISA. The R6G9 anti-CCL5 mAb does not cross-react with other mouse CC chemokines such as monocyte chemoattractant protein-1/CCL2 or macrophage-inflammatory protein-1␣/CCL3 or the mouse CXC chemokines IFN-␥-inducible protein-10/CXC chemokine ligand (CXCL)10 or monokine induced by interferon-␥/CXCL9 as determined by ELISA (28,29).…”

Section: Anti-ccl5 Mabmentioning

confidence: 99%

Antibody Targeting of the CC Chemokine Ligand 5 Results in Diminished Leukocyte Infiltration into the Central Nervous System and Reduced Neurologic Disease in a Viral Model of Multiple Sclerosis

Glass

Hickey

Hardison

et al. 2004

The Journal of Immunology

122

111

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Intracerebral infection of mice with mouse hepatitis virus, a member of the Coronaviridae family, reproducibly results in an acute encephalomyelitis that progresses to a chronic demyelinating disease. The ensuing neuropathology during the chronic stage of disease is primarily immune mediated and similar to that of the human demyelinating disease multiple sclerosis. Secretion of chemokines within the CNS signals the infiltration of leukocytes, which results in destruction of white matter and neurological impairment. The CC chemokine ligand (CCL)5 is localized in white matter tracts undergoing demyelination, suggesting that this chemokine participates in the pathogenesis of disease by attracting inflammatory cells into the CNS. In this study, we administer a mAb directed against CCL5 to mice with established mouse hepatitis virus-induced demyelination and impaired motor skills. Anti-CCL5 treatment decreased T cell accumulation within the CNS based, in part, on viral Ag specificity, indicating the ability to differentially target select populations of T cells. In addition, administration of anti-CCL5 improved neurological function and significantly (p ≤ 0.005) reduced the severity of demyelination and macrophage accumulation within the CNS. These results demonstrate that the severity of CNS disease can be reduced through the use of a neutralizing mAb directed against CCL5 in a viral model of demyelination.

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Acute and relapsing experimental autoimmune encephalomyelitis are regulated by differential expression of the CC chemokines macrophage inflammatory protein-1α and monocyte chemotactic protein-1

Cited by 228 publications

References 39 publications

Interfering with the CCL2–glycosaminoglycan axis as a potential approach to modulate neuroinflammation

Interfering with the CCL2–glycosaminoglycan axis as a potential approach to modulate neuroinflammation

G-CSF Therapy of Ongoing Experimental Allergic Encephalomyelitis Via Chemokine- and Cytokine-Based Immune Deviation

Antibody Targeting of the CC Chemokine Ligand 5 Results in Diminished Leukocyte Infiltration into the Central Nervous System and Reduced Neurologic Disease in a Viral Model of Multiple Sclerosis

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