Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P43026 (lipopolysaccharide)
 62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The CX3C-chemokine, fractalkine is reportedly to be expressed in the central nervous system, and up-regulated in certain pathological conditions, such as HIV encephalopathy and multiple sclerosis. In the present study, we examined the production of fractalkine and the expression of its receptor, CX3CR1 in murine glial and neuronal cell in vitro, and investigated its neuroprotective functions. Both fractalkine and CX3CR1 were expressed constitutively in neurons, microglia, and astrocytes. Neither the production of fractalkine nor its receptor expression was up-regulated by lipopolysaccharide (LPS), as measured by mRNA expression and protein synthesis. Fractalkine dose-dependently suppressed the production of nitric oxide (NO), interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha with activated microglia. It also significantly suppressed neuronal cell death induced by microglia activated with LPS and interferon-gamma, in a dose-dependent manner. These results suggest the possible functions of fractalkine as an intrinsic inhibitor against neurotoxicity by activated microglia.
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PMID:Production and neuroprotective functions of fractalkine in the central nervous system. 1285 May 72

Microglial activation has been implicated in various neurological disorders, including Alzheimer's disease, Parkinson's disease, multiple sclerosis, and HIV encephalopathy. Phytoestrogens have been shown to be neuroprotective in neurotoxicity models; however, their effect on microglia has not been well established. In the current study, we report that the soy phytoestrogens, genistein, daidzein, and coumestrol, decreased nitric oxide (NO) production induced by lipopolysaccharide (LPS) in the rat microglial cell line (HAPI). The levels of inducible NO synthase (iNOS) mRNA and protein expression were also reduced. Transcription factors known to govern iNOS expression including interferon regulatory factor-1 (IRF-1) and phosphorylated STAT1 were down regulated. These observations explain, at least in part, the inhibitory effect of phytoestrogens on NO production. The levels of monocyte chemoattractant protein-1 and interleukin-6 mRNA, proinflammatory chemokine and cytokine associated with various neurological disorders, were also reduced following LPS stimulation when HAPI cells were pretreated with phytoestrogens. Hence, genistein, daidzein, and coumestrol could serve as anti-inflammatory agents and may have beneficial effects in the treatment of neurodegenerative diseases.
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PMID:Phytoestrogens mediated anti-inflammatory effect through suppression of IRF-1 and pSTAT1 expressions in lipopolysaccharide-activated microglia. 2393 52