Diazepam inhibits HIV-1 Tat-induced migration of human microglia

• Published in: Journal of neurovirology Vol. 7; no. 5; pp. 481 - 486
• Main Authors: Lokensgard, J R, Hu, S, Hegg, C C, Thayer, S A, Gekker, G, Peterson, P K
• Format: Journal Article
• Language: English
• Published: United States Informa UK Ltd 01.10.2001
• Subjects: Adjuvants, Immunologic - pharmacology; Benzodiazepinones - pharmacology; Calcium Signaling - drug effects; Chemotaxis - drug effects; Clonazepam - pharmacology; Diazepam - pharmacology; Gene Products, tat - antagonists & inhibitors; Gene Products, tat - physiology; HIV-1 - drug effects; Human immunodeficiency virus 1; Humans; Microglia - drug effects; Microglia - virology; Nerve Tissue Proteins - drug effects; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - physiology; Receptors, CCR5 - biosynthesis; Receptors, CCR5 - genetics; Receptors, GABA-A - drug effects; Receptors, GABA-A - physiology; tat Gene Products, Human Immunodeficiency Virus; Up-Regulation - drug effects
• ISSN: 1355-0284; 1538-2443
• DOI: 10.1080/135502801753170345

During HIV-1 encephalitis, the chemotaxis-inducing activity of Tat may enhance the viral life cycle through recruitment of additional susceptible microglial cells to foci of infection. Benzodiazepines (BDZs) readily penetrate the blood-brain barrier and are known to possess anti-inflammatory properties. Pretreatment of human microglial cells with peripheral (Ro5-4864) and mixed (diazepam), but not central (clonazepam), benzodiazepine receptor ligands was found to potently suppress HIV-1 Tat-induced chemotaxis. Application of Tat to microglial cells evokes an increase in intracellular calcium concentration ([Ca 2+