Genomic and functional changes induced by the activation of the peripheralcannabinoid receptor CB2 in the promyelocytic cells HL-60 - Possible involvement of the CB2 receptor in cell differentiation

The function of the peripheral cannabinoid receptor (CB2), which is mainly expressed on hematopoietic cells, remains an enigma. In an attempt to decip her its role, we used Affymetrix(TM) DNA chips to investigate the gene expr ession profile of the promyelocytic cells HL-60 transfected with the CB2 re ceptor and activated with the cannabinoid agonist CP 55,940, Agonist exposu re of these cells led to an activation of a mitogen-activated protein kinas e cascade and a receptor desensitization, indicating a functional coupling of the transfected receptors. At the genomic level, activation of the CB2 r eceptors induced an up-regulation of nine genes involved in cytokine synthe sis, regulation of transcription, and cell differentiation. A majority of t hem are under the control of the transcription factor NF-kappa B, whose nuc lear translocation was demonstrated. Many features of the transcriptional e vents, reported here for the first time, appeared to be related to an activ ation of a cell differentiation program, suggesting that CB2 receptors coul d play a role in the initialization of cell maturation. Moreover, we showed that CB2-activated wild-type HL-60 cells developed properties usually foun d in host defense effector cells such as an enhanced release of chemotactic cytokines and an increased motility, characteristic of more mature cells o f the granulocytic-monocytic lineage.