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Interferon γ treatment increases endocannabinoid and related N-acylethanolamine levels in T84 human colon carcinoma cells
Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.ORCID iD: 0000-0002-2883-5603
Umeå University, Faculty of Science and Technology, Department of Chemistry.
Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.ORCID iD: 0000-0002-6658-7874
2019 (English)In: British Journal of Pharmacology, ISSN 0007-1188, E-ISSN 1476-5381, Vol. 176, no 10, p. 1470-1480Article in journal (Refereed) Published
Abstract [en]

Background and purpose: Endocannabinoids and related N-acylethanolamines (NAEs) are involved in regulation of gut function, but relatively little is known as to whether inflammatory cytokines such as IFN affect their levels. We have investigated this in vitro using cultures of T84 colon cancer cells.

Experimental approach: T84 cells, when cultured in monolayers, differentiate to form adult colonic crypt-like cells with excellent permeability barrier properties. The integrity of the permeability barrier in these monolayers was measured using transepithelial electrical resistance (TEER). NAE levels were determined by ultra-performance liquid chromatography-tandem mass spectrometric analysis. Expression of the enzymes involved in NAE and 2-arachidonoylglycerol (2-AG) turnover were assessed with qPCR.

Key results: IFN treatment for 8 or 24h increased levels of both endocannabinoids (anandamide and 2-AG) and the related NAEs. The treatment did not affect the rate of hydrolysis of either anandamide or palmitoylethanolamide by intact cells, and in both cases, fatty acid amide hydrolase (FAAH) rather than NAE-hydrolysing acid amidase (NAAA) was mainly responsible for the hydrolysis of these NAEs. IFN treatment reduced the TEER of the cells in a manner that was not prevented by inhibition of either FAAH or NAAA but was partially reversed by apical administration of the NAE palmitoylethanolamide.

Conclusion and implications: IFN treatment mobilized endocannabinoid and related NAE levels in T84 cells. However, blockade of anandamide or NAE hydrolysis was insufficient to negate the deleterious effects of this cytokine upon the permeability barrier of the cell monolayers.

Place, publisher, year, edition, pages
2019. Vol. 176, no 10, p. 1470-1480
National Category
Pharmacology and Toxicology
Identifiers
URN: urn:nbn:se:umu:diva-159393DOI: 10.1111/bph.14135ISI: 000466968400010PubMedID: 29313885OAI: oai:DiVA.org:umu-159393DiVA, id: diva2:1322240
Conference
8th European Workshop on Cannabinoid Research, Roehampton, England, United Kingdom, 31 August - 2 September, 2017
Available from: 2019-06-10 Created: 2019-06-10 Last updated: 2019-06-10Bibliographically approved

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Alhouayek, MireilleRankin, LindaGouveia-Figueira, Sandra C.Fowler, Christopher J

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Alhouayek, MireilleRankin, LindaGouveia-Figueira, Sandra C.Fowler, Christopher J
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