Autocrine and Paracrine Regulation of Lymphocyte CB2 Receptor Expression by TGF-beta

Biochem Biophys Res Commun. 2002 Jan 11;290(1):91-6. doi: 10.1006/bbrc.2001.6179.

Abstract

The marijuana-derived cannabinoid Delta(9)-tetrahydrocannabinol (THC) has been shown to be immunosuppressive. We report that THC induces the immunosuppressive cytokine TGF-beta by human peripheral blood lymphocytes (PBL). The ability of THC to stimulate TGF-beta production was blocked by the CB2 receptor specific antagonist SR144528 but not by the CB1 specific antagonist AM251. Furthermore, our data suggest that TGF-beta actively regulates lymphocyte CB2 receptor expression in an autocrine and paracrine manner. Whereas the addition of recombinant TGF-beta to PBL cultures downregulated CB2 receptor expression, anti-TGF-beta antibody treatment increased CB2 receptor expression. We conclude that one mechanism by which THC contributes to immune suppression is by stimulating an enhanced production of lymphocyte TGF-beta.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 1-Methyl-3-isobutylxanthine / pharmacology
  • Autocrine Communication
  • Blotting, Northern
  • Blotting, Western
  • Camphanes / pharmacology
  • Colforsin / pharmacology
  • Cyclic AMP / metabolism
  • Dose-Response Relationship, Drug
  • Down-Regulation
  • Dronabinol / pharmacology
  • Enzyme-Linked Immunosorbent Assay
  • GTP-Binding Proteins / metabolism
  • Gene Expression Regulation*
  • Humans
  • Immunoenzyme Techniques
  • Lymphocytes / metabolism*
  • Models, Biological
  • Paracrine Communication
  • Piperidines / pharmacology
  • Psychotropic Drugs / pharmacology
  • Pyrazoles / pharmacology
  • RNA / metabolism
  • Receptors, Cannabinoid
  • Receptors, Drug / biosynthesis*
  • Recombinant Proteins / metabolism
  • Transforming Growth Factor beta / metabolism*
  • Up-Regulation
  • Virulence Factors, Bordetella / pharmacology

Substances

  • Camphanes
  • Piperidines
  • Psychotropic Drugs
  • Pyrazoles
  • Receptors, Cannabinoid
  • Receptors, Drug
  • Recombinant Proteins
  • SR 144528
  • Transforming Growth Factor beta
  • Virulence Factors, Bordetella
  • Colforsin
  • AM 251
  • RNA
  • Dronabinol
  • Cyclic AMP
  • GTP-Binding Proteins
  • 1-Methyl-3-isobutylxanthine