Cannabinoid signalling in TNF-alpha induced IL-8 release

Mormina, Maria E., Thakur, Shori, Molleman, Areles, Whelan, Cliff J. and Baydoun, Anwar R. (2006) Cannabinoid signalling in TNF-alpha induced IL-8 release. European Journal of Pharmacology, 540 (1-3). pp. 183-190. ISSN 0014-2999

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The molecular events mediating the immunomodulatory properties of cannabinoids have remained largely unresolved. We have therefore investigated the molecular mechanism(s) through which R-(+)-[2,3-dihydro-5-methyl-3-[(morpholinyl)methyl] pyrrolo[1,2,3-de]-1,4-benzoxazinyl]-(1-napthanlenyl) methanone (WIN55212-2) modulate production of interleukin-8 (IL-8) in HT-29 cells. Release of IL-8 induced by tumor necrosis factor-alpha (TNF-alpha) was determined by enzyme-linked immunosorbent assay (ELISA). Changes in expression of inhibitory kappa B (IkappaB) were monitored by Western blotting and activation of nuclear factor-kappa B (NF-kappaB) was determined in electrophoretic mobility shift assay (EMSAs). TNF-alpha induced release of IL-8 was inhibited by WIN55212-2 which also blocked the degradation of IkappaB-alpha and activation of NF-kappaB induced by TNF-alpha. These data provide strong evidence that WIN55212-2 may modulate IL-8 release by negatively regulating the signaling cascade leading to the activation of NF-kappaB. These findings highlight a potential mechanism for the immunomodulatory properties of cannabinoids and contribute towards acquiring a clear understanding of the role of cannabinoids in inflammation.

Item Type: Article
Faculty \ School: Faculty of Science > School of Biological Sciences
Faculty of Science > School of Chemistry
Depositing User: Maru Mormina
Date Deposited: 22 Jun 2011 11:20
Last Modified: 24 Oct 2022 01:38
DOI: 10.1016/j.ejphar.2006.04.015

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