P.53 ARYL HYDROCARBON RECEPTOR SIGNALING PROTECTS MICE FROM INFLAMMATORY BOWEL DISEASE

2010 ◽  
Vol 42 ◽  
pp. S122
Author(s):  
I. Monteleone ◽  
A. Fabrizi ◽  
A. Rizzo ◽  
M. Sarra ◽  
F. Pallone ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Aryl Hydrocarbon Receptor ◽  
Bowel Disease ◽  
Receptor Signaling ◽  
Aryl Hydrocarbon ◽  
Inflammatory Bowel ◽  
P 53

The aryl hydrocarbon receptor in inflammatory bowel disease

2012 ◽  
Vol 28 (4) ◽  
pp. 310-313 ◽  
Author(s):  
Ivan Monteleone ◽  
Thomas T. MacDonald ◽  
Francesco Pallone ◽  
Giovanni Monteleone
Keyword(s):  
Inflammatory Bowel Disease ◽  
Aryl Hydrocarbon Receptor ◽  
Bowel Disease ◽  
Aryl Hydrocarbon ◽  
Inflammatory Bowel

scholarly journals An endogenous aryl hydrocarbon receptor ligand, ITE, induces regulatory T cells and ameliorates experimental colitis

2018 ◽  
Vol 315 (2) ◽  
pp. G220-G230 ◽  
Author(s):  
Jessica D. Abron ◽  
Narendra P. Singh ◽  
Manoj K. Mishra ◽  
Robert L. Price ◽  
Mitzi Nagarkatti ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
T Cells ◽  
Methyl Ester ◽  
Regulatory T Cells ◽  
Aryl Hydrocarbon Receptor ◽  
Inflammatory Cytokines ◽  
Acid Methyl Ester ◽  
Aryl Hydrocarbon ◽  
Acid Methyl ◽  
Inflammatory Bowel

Inflammatory bowel disease (IBD) is a chronic intestinal inflammatory condition that affects millions of people with high morbidity and health care costs. The precise etiology of IBD is unknown, but clear evidence suggests that intestinal inflammation is caused by an excessive immune response to mucosal antigens. Recent studies have shown that activation of the aryl hydrocarbon receptor (AhR) induces regulatory T cells (Tregs) and suppresses autoimmune diseases. In the current study, we investigated if a nontoxic ligand of AhR, 2-(1′ H-indole-3′-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE), can attenuate dextran sodium sulfate-induced colitis. Our studies demonstrated that in mice that received ITE treatment in vivo, colitis pathogenesis, including a decrease in body weight, was significantly reversed along with the systemic and intestinal inflammatory cytokines. ITE increased the expression of Tregs in spleen, mesenteric lymph nodes (MLNs), and colon lamina propria lymphocytes (cLPL) of mice with colitis when compared with controls. This induction of Tregs was reversed by AhR antagonist treatment in vitro. ITE treatment also increased dendritic cells (CD11c+) and decreased macrophages (F4/80+) from the spleen, MLNs, and cLPL in mice with colitis. ITE also reversed the systemic and intestinal frequency of CD4+T cells during colitis and suppressed inflammatory cytokines including IFN-γ, TNF-α, IL-17, IL-6, and IL-1 as well as induced IL-10 levels. These findings suggest that ITE attenuates colitis through induction of Tregs and reduction in inflammatory CD4+T cells and cytokines. Therefore, our work demonstrates that the nontoxic endogenous AhR ligand ITE may serve as a therapeutic modality to treat IBD.NEW & NOTEWORTHY We report the novel finding that activation of the aryl hydrocarbon receptor with the nontoxic ligand 2-(1′H-indole-3′-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE) induces regulatory T cells (Tregs) and suppresses inflammatory bowel disease (IBD). Our data suggest that ITE diminishes colitis pathology through induction of Tregs; reduces inflammatory cytokines, inflammation score, and macrophage frequency; and induces DCs resulting in amelioration of colitis. Therefore, nontoxic endogenous ITE promotes the induction of Tregs and may be useful for the treatment of IBD.

scholarly journals Increased expression of kynurenine aminotransferases mRNA in lymphocytes of patients with inflammatory bowel disease

2019 ◽  
Vol 12 ◽  
pp. 175628481988130 ◽  
Author(s):  
Ewa Dudzińska ◽  
Kinga Szymona ◽  
Renata Kloc ◽  
Paulina Gil-Kulik ◽  
Tomasz Kocki ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Active Phase ◽  
Serum Levels ◽  
Orphan Receptor ◽  
Aryl Hydrocarbon ◽  
Cytotoxic Compound ◽  
Inflammatory Bowel ◽  
Functional Shift ◽  
The Individual

Background: Complex interaction of genetic defects with environmental factors seems to play a substantial role in the pathogenesis of inflammatory bowel disease (IBD). Accumulating data implicate a potential role of disturbed tryptophan metabolism in IBD. Kynurenic acid (KYNA), a derivative of tryptophan (TRP) along the kynurenine (KYN) pathway, displays cytoprotective and immunomodulating properties, whereas 3-OH-KYN is a cytotoxic compound, generating free radicals. Methods: The expression of lymphocytic mRNA encoding enzymes synthesizing KYNA (KAT I–III) and serum levels of TRP and its metabolites were evaluated in 55 patients with IBD, during remission or relapse [27 patients with ulcerative colitis (UC) and 28 patients with Crohn’s disease (CD)] and in 50 control individuals. Results: The increased expression of KAT1 and KAT3 mRNA characterized the entire cohorts of patients with UC and CD, as well as relapse–remission subsets. Expression of KAT2 mRNA was enhanced in patients with UC and in patients with CD in remission. In the entire cohorts of UC or CD, TRP levels were lower, whereas KYN, KYNA and 3-OH-KYN were not altered. When analysed in subsets of patients with UC and CD (active phase–remission), KYNA level was significantly lower during remission than relapse, yet not versus control. Functionally, in the whole groups of patients with UC or CD, the TRP/KYN ratio has been lower than control, whereas KYN/KYNA and KYNA/3-OH-KYN ratios were not altered. The ratio KYN/3-OH-KYN increased approximately two-fold among all patients with CD; furthermore, patients with CD with relapse, manifested a significantly higher KYNA/3-OH-KYN ratio than patients in remission. Conclusion: The presented data indicate that IBD is associated with an enhanced expression of genes encoding KYNA biosynthetic enzymes in lymphocytes; however, additional mechanisms appear to influence KYNA levels. Higher metabolic conversion of serum TRP in IBD seems to be followed by the functional shift of KYN pathway towards the arm producing KYNA during exacerbation. We propose that KYNA, possibly via interaction with aryl hydrocarbon receptor or G-protein-coupled orphan receptor 35, may serve as a counter-regulatory mechanism, decreasing cytotoxicity and inflammation in IBD. Further longitudinal studies evaluating the individual dynamics of TRP and KYN pathway in patients with IBD, as well as the nature of precise mechanisms regulating KYNA synthesis, should be helpful in better understanding the processes underlying the observed changes.

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