title: Cannabinoids inhibit migration of microglial-like cells to the HIV protein Tat.
abstract: Microglia are a population of macrophage-like cells in the central nervous system (CNS) which, upon infection by the human immunodeficiency virus (HIV), secrete a plethora of inflammatory factors, including the virus-specified trans-activating protein Tat. Tat has been implicated in HIV neuropathogenesis since it elicits chemokines, cytokines, and a chemotactic response from microglia. It also harbors a β-chemokine receptor binding motif, articulating a mode by which it acts as a migration stimulus. Since select cannabinoids have anti-inflammatory properties, cross the blood-brain barrier, and target specific receptors, they have potential to serve as agents for dampening untoward neuroimmune responses. The aim of this study was to investigate the effect of select cannabinoids on the migration of microglial-like cells toward Tat. Using a mouse BV-2 microglial-like cell model, it was demonstrated that the exogenous cannabinoids Delta-9-tetrahydrocannabinol (THC) and CP55940 exerted a concentration-related reduction in the migration of BV-2 cells towards Tat. A similar inhibitory response was obtained when the endogenous cannabinoid 2-arachidonoylglycerol (2-AG) was used. The CB(2) receptor (CB2R) antagonist SR144528, but not the CB(1) receptor (CB1R) antagonist SR141716A, blocked this inhibition of migration. Similarly, CB2R knockdown with small interfering RNA reversed the cannabinoid-mediated inhibition. In addition, the level of the β-chemokine receptor CCR-3 was reduced and its intracellular compartmentation was altered. These results indicate that cannabinoid-mediated inhibition of BV-2 microglial-like cell migration to Tat is linked functionally to the CB2R. Furthermore, the results indicate that activation of the CB2R leads to altered expression and compartmentation of the β-chemokine receptor CCR-3.
authors: Department of Microbiology and Immunology, School of Medicine, Virginia Commonwealth University, 1101 E. Marshall St., Richmond, VA 23298, USA.
authors: Daniel
authors: D
authors: Fraga
authors: Erinn S
authors: ES
authors: Raborn
authors: Gabriela A
authors: GA
authors: Ferreira
authors: Guy A
authors: GA
authors: Cabral
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002186:Cannabinoids / Q000494:pharmacology*; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects*; D004591:Electrophoresis, Polyacrylamide Gel; D055785:Gene Knockdown Techniques; D051379:Mice; D017628:Microglia / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D018613:Microscopy, Confocal; D034741:RNA, Small Interfering; D060888:Real-Time Polymerase Chain Reaction; D020239:Receptor Cross-Talk / Q000187:drug effects / Q000276:immunology; D043885:Receptor, Cannabinoid, CB2 / Q000276:immunology / Q000378:metabolism*; D054397:Receptors, CCR3 / Q000276:immunology / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000276:immunology* / Q000378:metabolism
chemical_list: D002186:Cannabinoids; D034741:RNA, Small Interfering; D043885:Receptor, Cannabinoid, CB2; D054397:Receptors, CCR3; D054322:tat Gene Products, Human Immunodeficiency Virus