Stimulation of peripheral cannabinoid receptor CB2 induces MCP‐1 and IL‐8 gene expression in human promyelocytic cell line HL60

FEBS Letters

Derocq, Jean-Marie²  Le Fur, Gérard¹  Casellas, Pierre²  Segui, Michel²  Jbilo, Omar² 

[1] Sanofi Recherche, Direction Scientifique, rue de France, 75013 Paris, France;Sanofi Recherche, Ligne Immunologie, 371 rue du Prof. J. Blayac, F-34184 Montpellier Cedex 4, France

关键词: Monocyte chemotactic protein;    Interleukin 8;    Cannabinoid receptor;    MCP-1;    monocyte chemotactic protein 1;    IL-8;    Interleukin 8;    MIP-1α;    macrophage inhibitory protein 1α;    GRO-α;    growth regulatory oncogene α;    PTX;    pertussis toxin;   

DOI  :  10.1016/S0014-5793(99)00380-4

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Using the recently developed methodology of nucleic acid microarrays spotted with specific cDNAs probes belonging to different gene families, we showed for the first time that nanomolar concentrations of the cannabinoid ligand CP-55940 upregulated the expression of two different members of the chemokine gene family: the α-chemokine interleukin-8 (IL-8) and the β-chemokine monocyte chemotactic protein-1 (MCP-1), in the promyelocytic cell line HL60 transfected with peripheral cannabinoid receptors (CB2). These genomic modulations observed on large-scale cDNA arrays were first confirmed by Northern blot studies. Furthermore, ELISA evaluations in culture supernatants indicated that the cannabinoid-induced activation of these two chemokine genes was followed by enhanced expression and secretion of the corresponding proteins. These upregulations initially observed in transfected HL60 cells overexpressing CB2 receptors, also occurred in normal non-transfected HL60 cells. The enhancement of IL-8 and MCP-1 gene transcription and protein production was shown to be pertussis toxin sensitive attesting that this phenomenon was a G_i protein-coupled receptor-mediated process as expected for cannabinoid receptors. More specifically, the abolition of the cannabinoid-induced effect by the specific CB2 antagonist SR 144528 indicated a strict peripheral cannabinoid-mediated process. Altogether, our data highlight a possible new function of peripheral cannabinoid receptors in the modulation of immune and inflammatory responses.

【 授权许可】

Unknown