EG is recipient of an Ubbo Emmius Fellowship from the School of Behavioral and Cognitive Neurosciences (BCN), University of Groningen
Virodhamine and CP55,940 modulate cAMP production and IL-8 release in human bronchial epithelial cells
Article first published online: 17 FEB 2009
2007 British Pharmacological Society
British Journal of Pharmacology
Volume 151, Issue 7, pages 1041–1048, August 2007
How to Cite
Gkoumassi, E., Dekkers, B. G. J., Dröge, M. J., Elzinga, C. R. S., Schmidt, M., Meurs, H., Zaagsma, J. and Nelemans, S. A. (2007), Virodhamine and CP55,940 modulate cAMP production and IL-8 release in human bronchial epithelial cells. British Journal of Pharmacology, 151: 1041–1048. doi: 10.1038/sj.bjp.0707320
- Issue published online: 17 FEB 2009
- Article first published online: 17 FEB 2009
- (Received February 19, 2007, Revised March 26, 2007, Accepted April 17, 2007)
- human bronchial epithelium;
- tumour necrosis factor-α
Background and purpose:
We investigated expression of cannabinoid receptors and the effects of the endogenous cannabinoid virodhamine and the synthetic agonist CP55,940 on cAMP accumulation and interleukin-8 (IL-8) release in human bronchial epithelial cells.
Human bronchial epithelial (16HBE14o−) cells were used. Total mRNA was isolated and cannabinoid receptor mRNAs were detected by RT-PCR. Expression of CB1 and CB2 receptor proteins was detected with Western blotting using receptor-specific antibodies. cAMP accumulation was measured by competitive radioligand binding assay. IL-8 release was measured by ELISA.
CB1 and CB2 receptor mRNAs and proteins were found. Both agonists concentration-dependently decreased forskolin-induced cAMP accumulation. This effect was inhibited by the CB2 receptor antagonist SR144528, and was sensitive to Pertussis toxin (PTX), suggesting the involvement of CB2 receptors and Gi/o-proteins. Cell pretreatment with PTX unmasked a stimulatory component, which was blocked by the CB1 receptor antagonist SR141716A. CB2 receptor-mediated inhibition of cAMP production by virodhamine and CP55,940 was paralleled by inhibition of tumor necrosis factor-α (TNF-α) induced IL-8 release. This inhibition was insensitive to SR141716A. In the absence of agonist, SR144528 by itself reduced TNF-α induced IL-8 release.
Conclusions and implications:
Our results show for the first time that 16HBE14o− cells respond to virodhamine and CP55,940. CB1 and CB2 receptor subtypes mediated activation and inhibition of adenylyl cyclase, respectively. Stimulation of the dominant CB2 receptor signalling pathway diminished cAMP accumulation and TNF-α-induced IL-8 release. These observations may imply that cannabinoids exert anti-inflammatory properties in airways by modulating cytokine release.
British Journal of Pharmacology (2007) 151, 1041–1048; doi:10.1038/sj.bjp.0707320