Please use this identifier to cite or link to this item: https://doi.org/10.1111/j.1471-4159.2007.04535.x
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dc.titleDexamethasone suppresses monocyte chemoattractant protein-1 production via mitogen activated protein kinase phosphatase-1 dependent inhibition of Jun N-terminal kinase and p38 mitogen-activated protein kinase in activated rat microglia
dc.contributor.authorZhou, Yan
dc.contributor.authorLing, Eng-Ang
dc.contributor.authorDheen, S Thameem
dc.date.accessioned2020-01-20T06:40:39Z
dc.date.available2020-01-20T06:40:39Z
dc.date.issued2007-08-01
dc.identifier.citationZhou, Yan, Ling, Eng-Ang, Dheen, S Thameem (2007-08-01). Dexamethasone suppresses monocyte chemoattractant protein-1 production via mitogen activated protein kinase phosphatase-1 dependent inhibition of Jun N-terminal kinase and p38 mitogen-activated protein kinase in activated rat microglia. JOURNAL OF NEUROCHEMISTRY 102 (3) : 667-678. ScholarBank@NUS Repository. https://doi.org/10.1111/j.1471-4159.2007.04535.x
dc.identifier.issn00223042
dc.identifier.issn14714159
dc.identifier.urihttps://scholarbank.nus.edu.sg/handle/10635/163912
dc.description.abstractMicroglial cells release monocyte chemoattractant protein-1 (MCP-1) which amplifies the inflammation process by promoting recruitment of macrophages and microglia to inflammatory sites in several neurological diseases. In the present study, dexamethasone (Dex), an anti-inflammatory and immunosuppressive drug has been shown to suppress the mRNA and protein expression of MCP-1 in activated microglia resulting in inhibition of microglial migration. This has been further confirmed by the chemotaxis assay which showed that Dex or MCP-1 neutralization with its antibody inhibits the microglial recruitment towards the conditioned medium of lipopolysaccharide (LPS)-treated microglial culture. This study also revealed that the down-regulation of the MCP-1 mRNA expression by Dex in activated microglial cells was mediated via mitogen-activated protein kinase (MAPK) pathways. It has been demonstrated that Dex inhibited the phosphorylation of Jun N-terminal kinase (JNK) and p38 MAP kinases as well as c-jun, the JNK substrate in microglia treated with LPS. The involvement of JNK and p38 MAPK pathways in induction of MCP-1 production in activated microglial cells was confirmed as there was an attenuation of MCP-1 protein release when microglial cells were treated with inhibitors of JNK and p38. In addition, Dex induced the expression of MAP kinase phosphatase-1 (MKP-1), the negative regulator of JNK and p38 MAP kinases in microglial cells exposed to LPS. Blockade of MKP-1 expression by triptolide enhanced the phosphorylation of JNK and p38 MAPK pathways and the mRNA expression of MCP-1 in activated microglial cells treated with Dex. In summary, Dex inhibits the MCP-1 production and subsequent microglial cells migration to the inflammatory site by regulating MKP-1 expression and the p38 and JNK MAPK pathways. This study reveals that the MKP-1 and MCP-1 as novel mediators of biological effects of Dex may help developing better therapeutic strategies for the treatment of patients with neuroinflammatory diseases. © 2007 The Authors.
dc.language.isoen
dc.publisherWILEY
dc.sourceElements
dc.subjectScience & Technology
dc.subjectLife Sciences & Biomedicine
dc.subjectBiochemistry & Molecular Biology
dc.subjectNeurosciences
dc.subjectNeurosciences & Neurology
dc.subjectjun N-terminal kinase
dc.subjectmonocyte chemoattractant protein-1
dc.subjectmitogen-activated protein kinase phosphatase-1
dc.subjectmicroglia
dc.subjectneuroinflammation
dc.subjectglucocorticoids
dc.subjectp38
dc.subjectPROINFLAMMATORY CYTOKINE BIOSYNTHESIS
dc.subjectCENTRAL-NERVOUS-SYSTEM
dc.subjectMAP KINASE
dc.subjectMULTIPLE-SCLEROSIS
dc.subjectGLIAL-CELLS
dc.subjectKAPPA-B
dc.subjectSTIMULATED MACROPHAGES
dc.subjectCHEMOTACTIC PROTEIN-1
dc.subjectCHEMOKINE RECEPTORS
dc.subjectINDUCED EXPRESSION
dc.typeArticle
dc.date.updated2020-01-17T07:45:31Z
dc.contributor.departmentANATOMY
dc.contributor.departmentMECHANOBIOLOGY INSTITUTE
dc.description.doi10.1111/j.1471-4159.2007.04535.x
dc.description.sourcetitleJOURNAL OF NEUROCHEMISTRY
dc.description.volume102
dc.description.issue3
dc.description.page667-678
dc.description.placeUNITED KINGDOM
dc.published.statePublished
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