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TLR4 receptor expression and function in F11 dorsal root ganglion × neuroblastoma hybrid cells

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Hashemian, Sanaz Al Houayek, Mireille [UCL] Fowler, Christopher J

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 IFNγ 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: IFNγ treatment for 8 or 24 h 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. IFNγ 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: IFNγ 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.

Document type Article de périodique (Journal article) – Article de recherche
Access type Accès libre
Publication date 2017
Language Anglais
Journal information "Innate Immunity" - Vol. 23, no.8, p. 687-696 (2017)
Peer reviewed yes
Publisher SAGE Publications
issn 1753-4259
e-issn 1753-4267
Publication status Publié
Affiliation UCL - SSH/IACS - Institute of Analysis of Change in Contemporary and Historical Societies
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Bibliographic reference Hashemian, Sanaz ; Al Houayek, Mireille ; Fowler, Christopher J. TLR4 receptor expression and function in F11 dorsal root ganglion × neuroblastoma hybrid cells. In: Innate Immunity, Vol. 23, no.8, p. 687-696 (2017)
Permanent URL http://hdl.handle.net/2078.1/210203