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The role of CB1 in intestinal permeability and inflammation

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The role of CB1 in intestinal permeability and inflammation. / Karwad, Mustafa A.; Couch, Daniel G.; Theophilidou, Elena et al.
In: FASEB Journal, Vol. 31, No. 8, 08.2017, p. 3267-3277.

Research output: Contribution to Journal/MagazineJournal articlepeer-review

Harvard

Karwad, MA, Couch, DG, Theophilidou, E, Sarmad, S, Barrett, DA, Larvin, M, Wright, KL, Lund, JN & O'Sullivan, SE 2017, 'The role of CB1 in intestinal permeability and inflammation', FASEB Journal, vol. 31, no. 8, pp. 3267-3277. https://doi.org/10.1096/fj.201601346R

APA

Karwad, M. A., Couch, D. G., Theophilidou, E., Sarmad, S., Barrett, D. A., Larvin, M., Wright, K. L., Lund, J. N., & O'Sullivan, S. E. (2017). The role of CB1 in intestinal permeability and inflammation. FASEB Journal, 31(8), 3267-3277. https://doi.org/10.1096/fj.201601346R

Vancouver

Karwad MA, Couch DG, Theophilidou E, Sarmad S, Barrett DA, Larvin M et al. The role of CB1 in intestinal permeability and inflammation. FASEB Journal. 2017 Aug;31(8):3267-3277. Epub 2017 Apr 12. doi: 10.1096/fj.201601346R

Author

Karwad, Mustafa A. ; Couch, Daniel G. ; Theophilidou, Elena et al. / The role of CB1 in intestinal permeability and inflammation. In: FASEB Journal. 2017 ; Vol. 31, No. 8. pp. 3267-3277.

Bibtex

@article{d9f9ae9e04854ca0ba1641434e682704,
title = "The role of CB1 in intestinal permeability and inflammation",
abstract = "The endocannabinoid system has previously been shown to play a role in the permeability and inflammatory response of the human gut. The goal of our study was to determine the effects of endogenous anandamide (AEA) and 2-arachidonoyl glycerol (2-AG) on the permeability and inflammatory response of intestinal epithelium under normal, inflammatory, and hypoxic conditions. Human intestinal mucosa was modeled using Caco-2 cells. Human tissue was collected from planned colorectal resections. Accumulation of AEA and 2-AG was achieved by inhibiting their metabolizing enzymes URB597 (a fatty acid amide hydrolase inhibitor) and JZL184 (a monoacylglycerol lipase inhibitor). Inflammation and ischemia were simulated with TNF-α and IFN-γ and oxygen deprivation. Permeability changes were measured by transepithelial electrical resistance. The role of the CB1 receptor was explored using CB1 knockdown (CB1Kd) intestinal epithelial cells. Endocannabinoid levels were measured using liquid chromatography-mass spectrometry. Cytokine secretion was measured using multiplex and ELISA. URB597 and JZL184 caused a concentration-dependent increase in permeability via CB1 (P < 0.0001) and decreased cytokine production. Basolateral application of JZL184 decreased permeability via CB1 (P < 0.0001). URB597 and JZL184 increased the enhanced (worsened) permeability caused by inflammation and hypoxia (P < 0.0001 and P < 0.05). CB1Kd cells showed reduced permeability response to inflammation (P < 0.01) but not hypoxia. 2-AG levels were increased in response to inflammation and hypoxia in Caco-2 cells. In human mucosal tissue, inflammation increased the secretion of granulocyte macrophage-colony stimulating factor, IL-12, -13, and -15, which was prevented with ex vivo treatment with URB597 and JZL184, and was inhibited by a CB1 antagonist. The results of this study show that endogenous AEA and 2-AG production and CB1 activation play a key modulatory roles in normal intestinal mucosa permeability and in inflammatory and hypoxic conditions.-Karwad, M. A., Couch, D. G., Theophilidou, E., Sarmad, S., Barrett, D. A., Larvin, M., Wright, K. L., Lund, J. N., O'Sullivan, S. E. The role of CB1 in intestinal permeability and inflammation.",
keywords = "gut, endocannabinoids, anandamide, 2-AG, Intestine, PERMEABILITY BARRIER",
author = "Karwad, {Mustafa A.} and Couch, {Daniel G.} and Elena Theophilidou and Sarir Sarmad and Barrett, {David A.} and Michael Larvin and Wright, {Karen L} and Lund, {Jonathan N.} and O'Sullivan, {Saoirse E.}",
note = "{\textcopyright} FASEB.",
year = "2017",
month = aug,
doi = "10.1096/fj.201601346R",
language = "English",
volume = "31",
pages = "3267--3277",
journal = "FASEB Journal",
issn = "0892-6638",
publisher = "FASEB",
number = "8",

}

RIS

TY - JOUR

T1 - The role of CB1 in intestinal permeability and inflammation

AU - Karwad, Mustafa A.

AU - Couch, Daniel G.

AU - Theophilidou, Elena

AU - Sarmad, Sarir

AU - Barrett, David A.

AU - Larvin, Michael

AU - Wright, Karen L

AU - Lund, Jonathan N.

AU - O'Sullivan, Saoirse E.

N1 - © FASEB.

PY - 2017/8

Y1 - 2017/8

N2 - The endocannabinoid system has previously been shown to play a role in the permeability and inflammatory response of the human gut. The goal of our study was to determine the effects of endogenous anandamide (AEA) and 2-arachidonoyl glycerol (2-AG) on the permeability and inflammatory response of intestinal epithelium under normal, inflammatory, and hypoxic conditions. Human intestinal mucosa was modeled using Caco-2 cells. Human tissue was collected from planned colorectal resections. Accumulation of AEA and 2-AG was achieved by inhibiting their metabolizing enzymes URB597 (a fatty acid amide hydrolase inhibitor) and JZL184 (a monoacylglycerol lipase inhibitor). Inflammation and ischemia were simulated with TNF-α and IFN-γ and oxygen deprivation. Permeability changes were measured by transepithelial electrical resistance. The role of the CB1 receptor was explored using CB1 knockdown (CB1Kd) intestinal epithelial cells. Endocannabinoid levels were measured using liquid chromatography-mass spectrometry. Cytokine secretion was measured using multiplex and ELISA. URB597 and JZL184 caused a concentration-dependent increase in permeability via CB1 (P < 0.0001) and decreased cytokine production. Basolateral application of JZL184 decreased permeability via CB1 (P < 0.0001). URB597 and JZL184 increased the enhanced (worsened) permeability caused by inflammation and hypoxia (P < 0.0001 and P < 0.05). CB1Kd cells showed reduced permeability response to inflammation (P < 0.01) but not hypoxia. 2-AG levels were increased in response to inflammation and hypoxia in Caco-2 cells. In human mucosal tissue, inflammation increased the secretion of granulocyte macrophage-colony stimulating factor, IL-12, -13, and -15, which was prevented with ex vivo treatment with URB597 and JZL184, and was inhibited by a CB1 antagonist. The results of this study show that endogenous AEA and 2-AG production and CB1 activation play a key modulatory roles in normal intestinal mucosa permeability and in inflammatory and hypoxic conditions.-Karwad, M. A., Couch, D. G., Theophilidou, E., Sarmad, S., Barrett, D. A., Larvin, M., Wright, K. L., Lund, J. N., O'Sullivan, S. E. The role of CB1 in intestinal permeability and inflammation.

AB - The endocannabinoid system has previously been shown to play a role in the permeability and inflammatory response of the human gut. The goal of our study was to determine the effects of endogenous anandamide (AEA) and 2-arachidonoyl glycerol (2-AG) on the permeability and inflammatory response of intestinal epithelium under normal, inflammatory, and hypoxic conditions. Human intestinal mucosa was modeled using Caco-2 cells. Human tissue was collected from planned colorectal resections. Accumulation of AEA and 2-AG was achieved by inhibiting their metabolizing enzymes URB597 (a fatty acid amide hydrolase inhibitor) and JZL184 (a monoacylglycerol lipase inhibitor). Inflammation and ischemia were simulated with TNF-α and IFN-γ and oxygen deprivation. Permeability changes were measured by transepithelial electrical resistance. The role of the CB1 receptor was explored using CB1 knockdown (CB1Kd) intestinal epithelial cells. Endocannabinoid levels were measured using liquid chromatography-mass spectrometry. Cytokine secretion was measured using multiplex and ELISA. URB597 and JZL184 caused a concentration-dependent increase in permeability via CB1 (P < 0.0001) and decreased cytokine production. Basolateral application of JZL184 decreased permeability via CB1 (P < 0.0001). URB597 and JZL184 increased the enhanced (worsened) permeability caused by inflammation and hypoxia (P < 0.0001 and P < 0.05). CB1Kd cells showed reduced permeability response to inflammation (P < 0.01) but not hypoxia. 2-AG levels were increased in response to inflammation and hypoxia in Caco-2 cells. In human mucosal tissue, inflammation increased the secretion of granulocyte macrophage-colony stimulating factor, IL-12, -13, and -15, which was prevented with ex vivo treatment with URB597 and JZL184, and was inhibited by a CB1 antagonist. The results of this study show that endogenous AEA and 2-AG production and CB1 activation play a key modulatory roles in normal intestinal mucosa permeability and in inflammatory and hypoxic conditions.-Karwad, M. A., Couch, D. G., Theophilidou, E., Sarmad, S., Barrett, D. A., Larvin, M., Wright, K. L., Lund, J. N., O'Sullivan, S. E. The role of CB1 in intestinal permeability and inflammation.

KW - gut

KW - endocannabinoids

KW - anandamide

KW - 2-AG

KW - Intestine

KW - PERMEABILITY BARRIER

U2 - 10.1096/fj.201601346R

DO - 10.1096/fj.201601346R

M3 - Journal article

C2 - 28404744

VL - 31

SP - 3267

EP - 3277

JO - FASEB Journal

JF - FASEB Journal

SN - 0892-6638

IS - 8

ER -