期刊
MOLECULAR IMMUNOLOGY
卷 43, 期 14, 页码 2169-2179出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.molimm.2006.01.005
关键词
cannabinoids; T lymphocytes; migration; chemotaxis; signaling
资金
- NCI NIH HHS [CA109527] Funding Source: Medline
- NIAID NIH HHS [AI49140] Funding Source: Medline
- NIDA NIH HHS [DA15008] Funding Source: Medline
Cannabinoids have been shown to influence the immune system. However, their immunomodulatory effects have not been extensively studied. In this investigation, we have observed that both primary and Jurkat T cells express a functional cannabinoid receptor 2 (CB2). Furthermore, both the synthetic cannabinoids CP55,940 and WIN55,212-2, as well as the CB2-selective agonist JWH-015, caused a significant inhibition of the chemokine CXCL12-induced and CXCR4-mediated chemotaxis of Jurkat T cells, as well as their transendothelial migration. Involvement of the CB, receptor was further confirmed by partial reversal of the inhibition using the CB2-specific antagonist, AM630. Similarly, CP55,940 and JWH-015 inhibited the CXCL I 2-induced chemotaxis of primary CD4(+) and CD8(+) T lymphocytes. Further investigation of signaling studies to delineate the mechanism of inhibition revealed that cannabinoids enhance CXCL12-induced p44/42 MAP kinase activity. However, enhanced MAP kinase activity was not responsible for the inhibition of chemotaxis. This suggests that cannabinoids differentially regulate CXCR4-mediated migration and MAP kinase activation in T cells. Cannabinoids were also found to downregulate the PMA-enhanced enzyme activity of matrix metalloproteinase-9, which is known to play an important role in transendothelial migration. This study provides novel information regarding cannabinoid modulation of functional effects in T cells. (c) 2006 Elsevier Ltd. All rights reserved.
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