Genetic Variants of Fatty Acid Amide Hydrolase Modulate Acute Inflammatory Responses to Colitis in Adult Male Mice

Cannabinoids, including cannabis derived phytocannabinoids and endogenous cannabinoids (endocannabinoids), are typically considered anti-inflammatory. One such endocannabinoid is N-arachidonoylethanolamine (anandamide, AEA), which is metabolized by fatty acid amide hydrolase (FAAH). In humans, there...

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Autores principales:	Haley A. Vecchiarelli, Robert J. Aukema, Catherine Hume, Vincent Chiang, Maria Morena, Catherine M. Keenan, Andrei S. Nastase, Francis S. Lee, Quentin J. Pittman, Keith A. Sharkey, Matthew N. Hill
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	endocannabinoids colitis cytokines amygdala inflammation Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
Acceso en línea:	https://doaj.org/article/5bee354e39844c43a6f96c4715ec912f
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spelling	oai:doaj.org-article:5bee354e39844c43a6f96c4715ec912f2021-12-01T20:31:26ZGenetic Variants of Fatty Acid Amide Hydrolase Modulate Acute Inflammatory Responses to Colitis in Adult Male Mice1662-510210.3389/fncel.2021.764706https://doaj.org/article/5bee354e39844c43a6f96c4715ec912f2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fncel.2021.764706/fullhttps://doaj.org/toc/1662-5102Cannabinoids, including cannabis derived phytocannabinoids and endogenous cannabinoids (endocannabinoids), are typically considered anti-inflammatory. One such endocannabinoid is N-arachidonoylethanolamine (anandamide, AEA), which is metabolized by fatty acid amide hydrolase (FAAH). In humans, there is a loss of function single nucleotide polymorphism (SNP) in the FAAH gene (C385A, rs324420), that leads to increases in the levels of AEA. Using a mouse model with this SNP, we investigated how this SNP affects inflammation in a model of inflammatory bowel disease. We administered 2,4,6-trinitrobenzene sulfonic acid (TNBS) intracolonically, to adult male FAAH SNP mice and examined colonic macroscopic tissue damage and myeloperoxidase activity, as well as levels of plasma and amygdalar cytokines and chemokines 3 days after administration, at the peak of colitis. We found that mice possessing the loss of function alleles (AC and AA), displayed no differences in colonic damage or myeloperoxidase activity compared to mice with wild type alleles (CC). In contrast, in plasma, colitis-induced increases in interleukin (IL)-2, leukemia inhibitory factor (LIF), monocyte chemoattractant protein (MCP)-1, and tumor necrosis factor (TNF) were reduced in animals with an A allele. A similar pattern was observed in the amygdala for granulocyte colony stimulating factor (G-CSF) and MCP-1. In the amygdala, the mutant A allele led to lower levels of IL-1α, IL-9, macrophage inflammatory protein (MIP)-1β, and MIP-2 independent of colitis—providing additional understanding of how FAAH may serve as a regulator of inflammatory responses in the brain. Together, these data provide insights into how FAAH regulates inflammatory processes in disease.Haley A. VecchiarelliHaley A. VecchiarelliHaley A. VecchiarelliRobert J. AukemaRobert J. AukemaRobert J. AukemaCatherine HumeCatherine HumeCatherine HumeCatherine HumeVincent ChiangVincent ChiangVincent ChiangVincent ChiangMaria MorenaMaria MorenaMaria MorenaMaria MorenaCatherine M. KeenanCatherine M. KeenanCatherine M. KeenanAndrei S. NastaseAndrei S. NastaseAndrei S. NastaseFrancis S. LeeQuentin J. PittmanQuentin J. PittmanQuentin J. PittmanQuentin J. PittmanKeith A. SharkeyKeith A. SharkeyKeith A. SharkeyMatthew N. HillMatthew N. HillMatthew N. HillMatthew N. HillFrontiers Media S.A.articleendocannabinoidscolitiscytokinesamygdalainflammationNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571ENFrontiers in Cellular Neuroscience, Vol 15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	endocannabinoids colitis cytokines amygdala inflammation Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
spellingShingle	endocannabinoids colitis cytokines amygdala inflammation Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Haley A. Vecchiarelli Haley A. Vecchiarelli Haley A. Vecchiarelli Robert J. Aukema Robert J. Aukema Robert J. Aukema Catherine Hume Catherine Hume Catherine Hume Catherine Hume Vincent Chiang Vincent Chiang Vincent Chiang Vincent Chiang Maria Morena Maria Morena Maria Morena Maria Morena Catherine M. Keenan Catherine M. Keenan Catherine M. Keenan Andrei S. Nastase Andrei S. Nastase Andrei S. Nastase Francis S. Lee Quentin J. Pittman Quentin J. Pittman Quentin J. Pittman Quentin J. Pittman Keith A. Sharkey Keith A. Sharkey Keith A. Sharkey Matthew N. Hill Matthew N. Hill Matthew N. Hill Matthew N. Hill Genetic Variants of Fatty Acid Amide Hydrolase Modulate Acute Inflammatory Responses to Colitis in Adult Male Mice
description	Cannabinoids, including cannabis derived phytocannabinoids and endogenous cannabinoids (endocannabinoids), are typically considered anti-inflammatory. One such endocannabinoid is N-arachidonoylethanolamine (anandamide, AEA), which is metabolized by fatty acid amide hydrolase (FAAH). In humans, there is a loss of function single nucleotide polymorphism (SNP) in the FAAH gene (C385A, rs324420), that leads to increases in the levels of AEA. Using a mouse model with this SNP, we investigated how this SNP affects inflammation in a model of inflammatory bowel disease. We administered 2,4,6-trinitrobenzene sulfonic acid (TNBS) intracolonically, to adult male FAAH SNP mice and examined colonic macroscopic tissue damage and myeloperoxidase activity, as well as levels of plasma and amygdalar cytokines and chemokines 3 days after administration, at the peak of colitis. We found that mice possessing the loss of function alleles (AC and AA), displayed no differences in colonic damage or myeloperoxidase activity compared to mice with wild type alleles (CC). In contrast, in plasma, colitis-induced increases in interleukin (IL)-2, leukemia inhibitory factor (LIF), monocyte chemoattractant protein (MCP)-1, and tumor necrosis factor (TNF) were reduced in animals with an A allele. A similar pattern was observed in the amygdala for granulocyte colony stimulating factor (G-CSF) and MCP-1. In the amygdala, the mutant A allele led to lower levels of IL-1α, IL-9, macrophage inflammatory protein (MIP)-1β, and MIP-2 independent of colitis—providing additional understanding of how FAAH may serve as a regulator of inflammatory responses in the brain. Together, these data provide insights into how FAAH regulates inflammatory processes in disease.
format	article
author	Haley A. Vecchiarelli Haley A. Vecchiarelli Haley A. Vecchiarelli Robert J. Aukema Robert J. Aukema Robert J. Aukema Catherine Hume Catherine Hume Catherine Hume Catherine Hume Vincent Chiang Vincent Chiang Vincent Chiang Vincent Chiang Maria Morena Maria Morena Maria Morena Maria Morena Catherine M. Keenan Catherine M. Keenan Catherine M. Keenan Andrei S. Nastase Andrei S. Nastase Andrei S. Nastase Francis S. Lee Quentin J. Pittman Quentin J. Pittman Quentin J. Pittman Quentin J. Pittman Keith A. Sharkey Keith A. Sharkey Keith A. Sharkey Matthew N. Hill Matthew N. Hill Matthew N. Hill Matthew N. Hill
author_facet	Haley A. Vecchiarelli Haley A. Vecchiarelli Haley A. Vecchiarelli Robert J. Aukema Robert J. Aukema Robert J. Aukema Catherine Hume Catherine Hume Catherine Hume Catherine Hume Vincent Chiang Vincent Chiang Vincent Chiang Vincent Chiang Maria Morena Maria Morena Maria Morena Maria Morena Catherine M. Keenan Catherine M. Keenan Catherine M. Keenan Andrei S. Nastase Andrei S. Nastase Andrei S. Nastase Francis S. Lee Quentin J. Pittman Quentin J. Pittman Quentin J. Pittman Quentin J. Pittman Keith A. Sharkey Keith A. Sharkey Keith A. Sharkey Matthew N. Hill Matthew N. Hill Matthew N. Hill Matthew N. Hill
author_sort	Haley A. Vecchiarelli
title	Genetic Variants of Fatty Acid Amide Hydrolase Modulate Acute Inflammatory Responses to Colitis in Adult Male Mice
title_short	Genetic Variants of Fatty Acid Amide Hydrolase Modulate Acute Inflammatory Responses to Colitis in Adult Male Mice
title_full	Genetic Variants of Fatty Acid Amide Hydrolase Modulate Acute Inflammatory Responses to Colitis in Adult Male Mice
title_fullStr	Genetic Variants of Fatty Acid Amide Hydrolase Modulate Acute Inflammatory Responses to Colitis in Adult Male Mice
title_full_unstemmed	Genetic Variants of Fatty Acid Amide Hydrolase Modulate Acute Inflammatory Responses to Colitis in Adult Male Mice
title_sort	genetic variants of fatty acid amide hydrolase modulate acute inflammatory responses to colitis in adult male mice
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/5bee354e39844c43a6f96c4715ec912f
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Genetic Variants of Fatty Acid Amide Hydrolase Modulate Acute Inflammatory Responses to Colitis in Adult Male Mice

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