title: Cannabinoid inhibits HIV-1 Tat-stimulated adhesion of human monocyte-like cells to extracellular matrix proteins.
abstract: OBJECTIVE
  The aim of this study was to assess the effect of select cannabinoids on human immunodeficiency virus type 1 (HIV-1) transactivating (Tat) protein-enhanced monocyte-like cell adhesion to proteins of the extracellular matrix (ECM).
  
  
  METHODS
  Collagen IV, laminin, or an ECM gel was used to construct extracellular matrix layers. Human U937 monocyte-like cells were exposed to Tat in the presence of ∆(9)-tetrahydrocannabinol (THC), CP55,940, and other select cannabinoids. Cell attachment to ECM proteins was assessed using an adhesion assay.
  
  
  RESULTS
  THC and CP55,940 inhibited Tat-enhanced attachment of U937 cells to ECM proteins in a mode that was linked to the cannabinoid receptor type 2 (CB2R). The cannabinoid treatment of Tat-activated U937 cells was associated with altered β1-integrin expression and distribution of polymerized actin, suggesting a modality by which these cannabinoids inhibited adhesion to the ECM.
  
  
  CONCLUSIONS
  The blood-brain barrier (BBB) is a complex structure that is composed of cellular elements and an extracellular matrix (ECM). HIV-1 Tat promotes transmigration of monocytes across this barrier, a process that includes interaction with ECM proteins. The results indicate that cannabinoids that activate the CB2R inhibit the ECM adhesion process. Thus, this receptor has potential to serve as a therapeutic agent for ablating neuroinflammation associated with HIV-elicited influx of monocytes across the BBB.
authors.affiliation: Department of Microbiology and Immunology, Virginia Commonwealth University, School of Medicine, Richmond, VA 23298.
authors.forename: Erinn S
authors.initials: ES
authors.lastname: Raborn
authors.affiliation: Department of Microbiology and Immunology, Virginia Commonwealth University, School of Medicine, Richmond, VA 23298.
authors.forename: Melissa
authors.initials: M
authors.lastname: Jamerson
authors.affiliation: Department of Microbiology and Immunology, Virginia Commonwealth University, School of Medicine, Richmond, VA 23298.
authors.forename: Francine
authors.initials: F
authors.lastname: Marciano-Cabral
authors.affiliation: Department of Microbiology and Immunology, Virginia Commonwealth University, School of Medicine, Richmond, VA 23298. Electronic address: gacabral@vcu.edu.
authors.forename: Guy A
authors.initials: GA
authors.lastname: Cabral
mesh_terms: D001812:Blood-Brain Barrier / Q000187:drug effects; D063386:Cannabinoid Receptor Agonists / Q000737:chemistry*; D002448:Cell Adhesion; D024141:Collagen Type IV / Q000378:metabolism; D003511:Cyclohexanols / Q000737:chemistry; D013759:Dronabinol / Q000737:chemistry*; D005109:Extracellular Matrix / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D015497:HIV-1; D006801:Humans; D007249:Inflammation / Q000188:drug therapy; D007797:Laminin / Q000378:metabolism; D009000:Monocytes / Q000166:cytology* / Q000187:drug effects / Q000821:virology*; D043885:Receptor, Cannabinoid, CB2 / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry; D020298:U937 Cells; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000737:chemistry*
chemical_list: C588309:CNR2 protein, human; D063386:Cannabinoid Receptor Agonists; D024141:Collagen Type IV; D003511:Cyclohexanols; D016326:Extracellular Matrix Proteins; D007797:Laminin; D043885:Receptor, Cannabinoid, CB2; D011994:Recombinant Proteins; D054322:tat Gene Products, Human Immunodeficiency Virus; D013759:Dronabinol; C054649:3-(2-hydroxy-4-(1,1-dimethylheptyl)phenyl)-4-(3-hydroxypropyl)cyclohexanol
keywords: 2-Arachidonoylglycerol (PubChem CID: 5282280); Arachidonyl-2-chloroethylamide (PubChem CID: 5311006); CP55,940 (PubChem CID: 104895); Cannabinoid; Cell adhesion; Extracellular matrix; HIV; Monocyte-like cells; SR141716A (PubChem CID: 104850); SR144528 (PubChem CID: 3081355); Tat; U937 cells; abnormal cannabidiol (PubChem CID: 3060519); ∆(9)-tetrahydrocannabinol (PubChem CID: 16078)
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