Please use this identifier to cite or link to this item: https://scholarbank.nus.edu.sg/handle/10635/163912
Title: 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
Authors: Zhou, Yan 
Ling, Eng-Ang 
Dheen, S Thameem 
Keywords: Science & Technology
Life Sciences & Biomedicine
Biochemistry & Molecular Biology
Neurosciences
Neurosciences & Neurology
jun N-terminal kinase
monocyte chemoattractant protein-1
mitogen-activated protein kinase phosphatase-1
microglia
neuroinflammation
glucocorticoids
p38
PROINFLAMMATORY CYTOKINE BIOSYNTHESIS
CENTRAL-NERVOUS-SYSTEM
MAP KINASE
MULTIPLE-SCLEROSIS
GLIAL-CELLS
KAPPA-B
STIMULATED MACROPHAGES
CHEMOTACTIC PROTEIN-1
CHEMOKINE RECEPTORS
INDUCED EXPRESSION
Issue Date: 1-Aug-2007
Publisher: WILEY
Citation: Zhou, 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.
Abstract: Microglial 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.
Source Title: JOURNAL OF NEUROCHEMISTRY
URI: https://scholarbank.nus.edu.sg/handle/10635/163912
ISSN: 00223042
14714159
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