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This Article Full Text Full Text (PDF) All Versions of this Article: 294/3/H1145    most recent 01328.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (7) Citing Articles via Google Scholar Google Scholar Articles by Montecucco, F. Articles by Steffens, S. Search for Related Content PubMed PubMed Citation Articles by Montecucco, F. Articles by Steffens, S.

CB₂ cannabinoid receptor agonist JWH-015 modulates human monocyte migration through defined intracellular signaling pathways

Division of Cardiology, Foundation for Medical Researches, University Hospital, Geneva, Switzerland

Submitted 12 November 2007 ; accepted in final form 2 January 2008

Recruitment of leukocytes to inflammatory sites is crucial in the pathogenesis of chronic inflammatory diseases. The aim of this study was to investigate if activation of CB₂ cannabinoid receptors would modulate the chemotactic response of human monocytes. Human monocytes treated with the CB₂ agonist JWH-015 for 12–18 h showed significantly reduced migration to chemokines CCL2 and CCL3, associated with reduced mRNA and surface expression of their receptors CCR2 and CCR1. The induction of ICAM-1 in response to IFN- was inhibited by JWH-015. Moreover, JWH-015 cross-desensitized human monocytes for migration in response to CCL2 and CCL3 by its own chemoattractant properties. The CB₂-selective antagonist SR-144528, but not the CB₁ antagonist SR-147778, reversed JWH-015-induced actions, whereas the CB₂ agonist JWH-133 mimicked the effects of JWH-015. The investigation of underlying pathways revealed the involvement of phosphatidylinositol 3-kinase/Akt and ERK1/2 but not p38 MAPK. In conclusion, selective activation of CB₂ receptors modulates chemotaxis of human monocytes, which might have crucial effects in chronic inflammatory disorders such as atherosclerosis or rheumatoid arthritis.

chemokines; chemokine receptors; intracellular adhesion molecule-1; chronic inflammation; atherosclerosis

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