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

Abstract

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+)]i) that rapidly desensitizes the cells. Diazepam's inhibitory effect was associated with its ability to block Tat-induced [Ca(2+)]i mobilization. These data support the notion that through their effects on microglia, peripheral BDZ receptor ligands could alter the neuropathogenesis of HIV-1.