Abstract
Diseases related to inflammation are a major cause of morbidity and mortality throughout the world and affect the functions of several tissues. The pathophysiology of these diseases involves release of many pro-inflammatory cytokines, such as TNF and IL-1, in addition to anti-inflammatory molecules. Recent studies have demonstrated that neuroimmune interactions are important in the initiation and progress of inflammatory processes. TNF, IL-1 and neuropeptides such as substance P and neurotensin stimulate the release of chemokines, in particular IL-8, a potent neutrophil chemoattractant. Expression of IL-8 is regulated mainly by the transcription factors NF-kappaB, activating protein-1 and CCAAT/enhancer-binding proteins. Recent exciting results indicate that the Rho family of small GTP-binding proteins plays an important role in the expression of NF-kappaB-dependent genes and migration of leukocytes. These results suggest that these proteins may represent a potential therapeutic target to treat several inflammatory states.
MeSH terms
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Animals
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Anti-Inflammatory Agents / pharmacology*
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Anti-Inflammatory Agents / therapeutic use
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Chemokines / physiology
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Cytokines / metabolism
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Drug Design*
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Drug Evaluation, Preclinical
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Enzyme Activation / drug effects
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Farnesyltranstransferase / antagonists & inhibitors
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Gene Expression Regulation / drug effects
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Humans
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Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology
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Inflammation / drug therapy*
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Inflammation / enzymology
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Inflammation / physiopathology
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Interleukin-8 / genetics
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Interleukin-8 / physiology
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MAP Kinase Signaling System / drug effects
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MAP Kinase Signaling System / physiology
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Macrophage Activation
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NF-kappa B / physiology
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Phosphorylation / drug effects
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Protein Prenylation / drug effects
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Protein Processing, Post-Translational / drug effects
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Rats
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Signal Transduction / drug effects
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Signal Transduction / physiology
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rho GTP-Binding Proteins / antagonists & inhibitors*
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rho GTP-Binding Proteins / genetics
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rho GTP-Binding Proteins / physiology
Substances
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Anti-Inflammatory Agents
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Chemokines
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Cytokines
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Hydroxymethylglutaryl-CoA Reductase Inhibitors
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Interleukin-8
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NF-kappa B
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Farnesyltranstransferase
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rho GTP-Binding Proteins