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Life Sci. 2014 May 28;104(1-2):15-23. doi: 10.1016/j.lfs.2014.04.008. Epub 2014 Apr 15.

Cannabinoid inhibits HIV-1 Tat-stimulated adhesion of human monocyte-like cells to extracellular matrix proteins.

Author information

1
Department of Microbiology and Immunology, Virginia Commonwealth University, School of Medicine, Richmond, VA 23298.
2
Department of Microbiology and Immunology, Virginia Commonwealth University, School of Medicine, Richmond, VA 23298. Electronic address: gacabral@vcu.edu.

Abstract

AIMS:

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).

MAIN 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.

KEY FINDINGS:

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.

SIGNIFICANCE:

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.

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)

PMID:
24742657
PMCID:
PMC4089388
DOI:
10.1016/j.lfs.2014.04.008
[Indexed for MEDLINE]
Free PMC Article

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