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Reduced endocannabinoid immune modulation by a common cannabinoid 2 (CB2) receptor gene polymorphism: possible risk for autoimmune disorders.
J Leukoc Biol 2005; 78(1):231-8JL

Abstract

Immune system responsiveness results from numerous factors, including endogenous cannabinoid signaling in immunocytes termed the "immunocannabinoid" system. This system can be an important signaling pathway for immune modulation. To assess the immunomodulating role of the cannabinoid 2 (CB2) receptor, we sought polymorphisms in the human gene, identified a common dinucleotide polymorphism, and investigated its effect on endocannabinoid-induced inhibition of T lymphocyte proliferation. The CB2 cDNA 188-189 GG/GG polymorphism predicts the substitution of glutamine at amino acid position 63 by arginine. T lymphocytes from CB2 188-189 GG/GG homozygotes had approximately twofold reduction of endocannabinoid-induced inhibition of proliferation compared with cells from CB2 188-189 AA/AA homozygotes. In GG/GG subjects, the reduced endocannabinoid inhibitory response was highly significant for N-arachidonylglycine and nearly significant for 2-arachidonylglycerol, and a specific CB2 receptor antagonist partially blocked these effects. Also, patients with autoimmune diseases had an increased prevalence of the homozygous GG/GG genotype. Collectively, these results demonstrate reduced endogenous fatty acid amide immunomodulatory responses in individuals with the CB2 188-189 GG/GG genotype and suggest that this CB2 gene variation may be a risk factor for autoimmunity. The results also support the proposition that the CB2 receptor may represent a novel pharmacological target for selective agonists designed to suppress autoreactive immune responses while avoiding CB1 receptor-mediated cannabinoid adverse effects.

Authors+Show Affiliations

Department of Molecular and Experimental Medicine, The Scripps Research Institute (MEM-215), La Jolla, CA 92037, USA. jcsipe@scripps.eduNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

15845647

Citation

Sipe, Jack C., et al. "Reduced Endocannabinoid Immune Modulation By a Common Cannabinoid 2 (CB2) Receptor Gene Polymorphism: Possible Risk for Autoimmune Disorders." Journal of Leukocyte Biology, vol. 78, no. 1, 2005, pp. 231-8.
Sipe JC, Arbour N, Gerber A, et al. Reduced endocannabinoid immune modulation by a common cannabinoid 2 (CB2) receptor gene polymorphism: possible risk for autoimmune disorders. J Leukoc Biol. 2005;78(1):231-8.
Sipe, J. C., Arbour, N., Gerber, A., & Beutler, E. (2005). Reduced endocannabinoid immune modulation by a common cannabinoid 2 (CB2) receptor gene polymorphism: possible risk for autoimmune disorders. Journal of Leukocyte Biology, 78(1), pp. 231-8.
Sipe JC, et al. Reduced Endocannabinoid Immune Modulation By a Common Cannabinoid 2 (CB2) Receptor Gene Polymorphism: Possible Risk for Autoimmune Disorders. J Leukoc Biol. 2005;78(1):231-8. PubMed PMID: 15845647.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Reduced endocannabinoid immune modulation by a common cannabinoid 2 (CB2) receptor gene polymorphism: possible risk for autoimmune disorders. AU - Sipe,Jack C, AU - Arbour,Nathalie, AU - Gerber,Alexandra, AU - Beutler,Ernest, Y1 - 2005/04/21/ PY - 2005/4/23/pubmed PY - 2005/9/9/medline PY - 2005/4/23/entrez SP - 231 EP - 8 JF - Journal of leukocyte biology JO - J. Leukoc. Biol. VL - 78 IS - 1 N2 - Immune system responsiveness results from numerous factors, including endogenous cannabinoid signaling in immunocytes termed the "immunocannabinoid" system. This system can be an important signaling pathway for immune modulation. To assess the immunomodulating role of the cannabinoid 2 (CB2) receptor, we sought polymorphisms in the human gene, identified a common dinucleotide polymorphism, and investigated its effect on endocannabinoid-induced inhibition of T lymphocyte proliferation. The CB2 cDNA 188-189 GG/GG polymorphism predicts the substitution of glutamine at amino acid position 63 by arginine. T lymphocytes from CB2 188-189 GG/GG homozygotes had approximately twofold reduction of endocannabinoid-induced inhibition of proliferation compared with cells from CB2 188-189 AA/AA homozygotes. In GG/GG subjects, the reduced endocannabinoid inhibitory response was highly significant for N-arachidonylglycine and nearly significant for 2-arachidonylglycerol, and a specific CB2 receptor antagonist partially blocked these effects. Also, patients with autoimmune diseases had an increased prevalence of the homozygous GG/GG genotype. Collectively, these results demonstrate reduced endogenous fatty acid amide immunomodulatory responses in individuals with the CB2 188-189 GG/GG genotype and suggest that this CB2 gene variation may be a risk factor for autoimmunity. The results also support the proposition that the CB2 receptor may represent a novel pharmacological target for selective agonists designed to suppress autoreactive immune responses while avoiding CB1 receptor-mediated cannabinoid adverse effects. SN - 0741-5400 UR - https://www.unboundmedicine.com/medline/citation/15845647/Reduced_endocannabinoid_immune_modulation_by_a_common_cannabinoid_2__CB2__receptor_gene_polymorphism:_possible_risk_for_autoimmune_disorders_ L2 - https://doi.org/10.1189/jlb.0205111 DB - PRIME DP - Unbound Medicine ER -