Rho GTPases as therapeutic targets for the treatment of inflammatory diseases.
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.
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D018925:Chemokines / Q000502:physiology; D016207:Cytokines / Q000378:metabolism; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D004789:Enzyme Activation / Q000187:drug effects; D051231:Farnesyltranstransferase / Q000037:antagonists & inhibitors; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D007249:Inflammation / Q000188:drug therapy* / Q000201:enzymology / Q000503:physiopathology; D016209:Interleukin-8 / Q000235:genetics / Q000502:physiology; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology; D008262:Macrophage Activation; D016328:NF-kappa B / Q000502:physiology; D010766:Phosphorylation / Q000187:drug effects; D017368:Protein Prenylation / Q000187:drug effects; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D020741:rho GTP-Binding Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000502:physiology
D000893:Anti-Inflammatory Agents; D018925:Chemokines; D016207:Cytokines; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D016209:Interleukin-8; D016328:NF-kappa B; D051231:Farnesyltranstransferase; D020741:rho GTP-Binding Proteins