Inflammatory Bowel Disease G-Prote in Coupled Receptors (GPCRs) Expression Profiling with Microfluidic Cards

Taquet, Nathalie; Philippe, Claude; Reimund, Jean‐Marie; Muller, Christian D.

doi:10.5772/28207

Cited by 5 publications

(8 citation statements)

References 31 publications

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“…Consistent with this, TAAR1 has been proposed to play a role in the susceptibility to fibromyalgia (Smith et al, 2012), TAAR6 implicated in treatment outcomes 598 in asthma (Chang et al, 2015), and TAAR2, TAAR5, and TAAR9 among the most highly upregulated genes in the inflamed zones of patients with Crohn disease (Taquet et al, 2012), an effect that allowed discrimination of these patients from those with irritable bowel syndrome. As previously indicated, two recent unbiased metabolomic studies have also identified elevated endogenous TAAR1 ligands in Crohn disease fecal samples (Jacobs et al, 2016;Santoru et al, 2017).…”

Section: Effects In the Peripherymentioning

confidence: 75%

Trace Amines and Their Receptors

Gainetdinov¹,

Hoener²,

Berry³

2018

Pharmacol Rev

301

287

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Section: Effects In the Peripherymentioning

confidence: 75%

Trace Amines and Their Receptors

Gainetdinov¹,

Hoener²,

Berry³

2018

Pharmacol Rev

301

287

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“…Taken together, these findings provide compelling evidence for an important role of 5-HT in gut inflammation. Despite the importance of its cognate receptors in 5-HT signaling, only scattered observations about 5-HTRs in IBD have been previously reported by a handful of studies (21, 22).…”

mentioning

confidence: 99%

Characterization of Serotonin Signaling Components in Patients with Inflammatory Bowel Disease

Shajib

Chauhan

Adeeb

et al. 2018

Journal of the Canadian Association of Gastroenterology

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Background Tryptophan hydroxylase (TPH)1 catalyzes the biosynthesis of serotonin (5-hydroxytrptamine; 5-HT) in enterochromaffin (EC) cells, the predominant source of gut 5-HT. Secreted 5-HT regulates various gut functions through diverse 5-HT receptor (5-HTR) families, and 5-HT transporter (5-HTT) sequesters its activity via uptake into surrounding cells. In inflammatory bowel disease (IBD) mucosal 5-HT signaling is altered, including upregulated EC cell numbers and 5-HT levels. We examined key mucosal 5-HT signaling components and blood 5-HT levels and, as part of a pilot study, investigated the association between 5-HTT gene-linked polymorphic region (5HTTLPR) and Crohn’s disease (CD). Methods In the context of inflammation, colonic expressions of TPH1, 5-HTT and 5-HTRs were studied in CD patients (n=15) and healthy controls (HC; n=10) using quantitative polymerase chain reaction (qPCR). We also investigated 5HTTLPR in 40 CD patients and HC utilizing PCR and measured platelet-poor plasma (PPP) and plasma 5-HT concentrations. Results Compared with HC, inflammation in CD patients was associated with elevated TPH1, 5-HTR3, 5-HTR4, 5-HTR7 and downregulated 5-HTT expressions. In our second cohort of participants, significantly higher PPP and plasma 5-HT levels and higher S-genotype (L/S+S/S) than L/L genotype were observed in CD patients compared with HC. Conclusion Our results suggest that augmented mucosal 5-HT signaling and specific 5-HTTLPR genotype–associated decreased efficiency in 5-HT reuptake, the latter through increased 5-HT availability, may contribute to inflammation in CD patients. These findings revealed important information on various components of 5-HT signaling in intestinal inflammation which may ultimately lead to effective strategies targeting this pathway in IBD.

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Section: Taars and The Immune Systemmentioning

confidence: 99%

“…Despite these identified changes in TAAR ligands, there appears to be only a single study that has identified possible roles of TAARs in IBD ( Taquet et al, 2012 ). Here, in an unbiased microarray screen, TAAR2, TAAR5, and TAAR9 were found to be among the most highly upregulated genes in biopsies from inflamed regions of CD patients, and contributed to the separation of CD patients from those with irritable bowel syndrome ( Taquet et al, 2012 ). Although neither PEA nor TYR are agonists at TAAR2, the aforementioned heterodimerization of TAAR2 with TAAR1 could provide a link between the altered TYR and PEA metabolomic profiles and TAAR2 over-expression, both of which allow discrimination of IBD populations.…”

Section: Taars and The Immune Systemmentioning

confidence: 99%

Trace Amine-Associated Receptors as Novel Therapeutic Targets for Immunomodulatory Disorders

Christian

Berry

2018

Front. Pharmacol.

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Trace amines and their receptors (trace amine-associated receptors; TAARs) are an emerging pharmacological target for the treatment of human disorders. While most studies have focused on their therapeutic potential for neurologic and psychiatric disorders, TAARs are also expressed throughout the periphery, including prominent expression in human leukocytes. Furthermore, recent independent, unbiased metabolomic studies have consistently identified one or more TAAR ligands as potential etiologic factors in inflammatory bowel disease (IBD). The putative role of TAARs in diseases such as IBD that are associated with hyperactive immune responses has not, however, previously been systematically addressed. Here, we review the current state of the knowledge of the effects of TAARs on leukocyte function, in particular in the context of mucosal epithelial cells that interface with the environment; developing a model whereby TAARs may be considered as a novel therapeutic target for disorders associated with dysregulated immune responses to environmental factors. In this model, we hypothesize that altered trace amine homeostasis results in hyperactivity of the immune system. Such loss of homeostasis can occur through many different mechanisms including TAAR polymorphisms and altered trace amine load due to changes in host synthesis and/or degradative enzymes, diet, or microbial dysbiosis. The resulting alterations in TAAR functioning can then lead to a loss of homeostasis of leukocyte chemotaxis, differentiation, and activation, as well as an altered ability of members of the microbiota to adhere to and penetrate the epithelial cell layers. Such changes would generate a pro-inflammatory state at mucosal epithelial barrier layers that can manifest as clinical symptomatology such as that seen in IBD. These alterations may also have the potential to induce systemic effects, which could possibly contribute to immunomodulatory disorders in other systems, including neurological diseases.

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Inflammatory Bowel Disease G-Prote in Coupled Receptors (GPCRs) Expression Profiling with Microfluidic Cards

Cited by 5 publications

References 31 publications

Trace Amines and Their Receptors

Trace Amines and Their Receptors

Characterization of Serotonin Signaling Components in Patients with Inflammatory Bowel Disease

Trace Amine-Associated Receptors as Novel Therapeutic Targets for Immunomodulatory Disorders

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