Tryptophan Metabolism Activates Aryl Hydrocarbon Receptor-Mediated Pathway To Promote HIV-1 Infection and Reactivation

Sun, Li; Sun, Wei‐Zen; Ma, Li; Han, Yang; Jin, Xia; Zhao, Quan; Li, Taisheng; Lu, Hongzhou; Qiu, Xiu; Wang, Jianhua

doi:10.1128/mbio.02591-19

Cited by 29 publications

(25 citation statements)

References 81 publications

(115 reference statements)

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“…Moreover, the binding of AHR with Tat viral protein facilitates the recruitment of positive transcription factors to viral promoters. These findings elucidate a previously unappreciated mechanism through which cellular Trp metabolites affect HIV pathogenesis, and also suggest that AHR signaling may be targeted to modulate HIV-1 infection ( 115 ).…”

Section: Ahr and Viral Infectionssupporting

confidence: 52%

“…Unusual high levels of Kyn have been detected in association with accelerated HIV-1 pathogenesis, but the molecular mechanism behind this observation remains unclear. However, it was recently reported that AHR is activated by Trp metabolites to favor HIV-1 infection and reactivation ( 115 ), suggesting a novel role for AHR in AIDS. AHR directly binds to the HIV-1 5′ long terminal repeat (5′-LTR) to activate viral transcription.…”

Section: Ahr and Viral Infectionsmentioning

confidence: 99%

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The Aryl Hydrocarbon Receptor as a Modulator of Anti-viral Immunity

2021

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The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor, which interacts with a wide range of organic molecules of endogenous and exogenous origin, including environmental pollutants, tryptophan metabolites, and microbial metabolites. The activation of AHR by these agonists drives its translocation into the nucleus where it controls the expression of a large number of target genes that include the AHR repressor (AHRR), detoxifying monooxygenases (CYP1A1 and CYP1B1), and cytokines. Recent advances reveal that AHR signaling modulates aspects of the intrinsic, innate and adaptive immune response to diverse microorganisms. This review will focus on the increasing evidence supporting a role for AHR as a modulator of the host response to viral infection.

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Section: Ahr and Viral Infectionssupporting

confidence: 52%

Section: Ahr and Viral Infectionsmentioning

confidence: 99%

The Aryl Hydrocarbon Receptor as a Modulator of Anti-viral Immunity

2021

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“…Moreover, rats with decreased intake of tryptophan had higher running performance (Yamamoto & Newsholme, 2003). Trp metabolites acting on the metabolic crossroad interconnecting different organs exert various beneficial effects (Le Floc'h et al., 2011; Roager & Licht, 2018) in a multiple of disorders, including central nervous system disorders, autoimmune diseases, and cancer (Zhou et al., 2019). Under inflammatory conditions, most Trp is diverted to produce Kyn and its metabolites kynurenine acid (KYNA) (Keszthelyi et al., 2012) with neuroprotective roles (Lim et al., 2017).…”

Section: Introductionmentioning

confidence: 99%

Tryptophan in the diet ameliorates motor deficits in a rotenone‐induced rat Parkinson's disease model via activating the aromatic hydrocarbon receptor pathway

et al. 2021

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Background and purpose: Parkinson's disease (PD), a common neurodegenerative disorder with motor and nonmotor symptoms, does not have effective treatments.Dietary tryptophan (Trp) supplementation has potential benefits for the treatment of multiple disorders. However, whether additional Trp in the diet could be beneficial for PD remains to beinvestigated. In the present study, the neuroprotective role of dietary Trp on a rotenone-induced rat model of PD was determined. Methods:The rotenone was injected to build the PD model, and then the rats were treated with Trp in the diet. And then, an open field test, western blot analysis, and enzyme linked immunosorbent assay (ELISA) were performed. Results:We observed that dietary Trp significantly ameliorated impaired motor function, upregulated tyrosine hydroxylase expression, inhibited the nuclear transport of Nuclear factor-kappa B (NF-κB) in substantia nigra (SN), and downregulated the protein levels of IL-1β, IL-6, and TNF-α in serum in rotenone-treated rats. However, these patterns were reversed in response to treatment with ampicillin, an agent that can clean intestinal Trp metabolism flora. Moreover, after using CH223191, an inhibitor of the aromatic hydrocarbon receptor (AhR) pathway, dietary Trp could not exert neuroprotective roles in the rotenone-induced rat model of PD. Conclusion:These results suggest that Trp in the diet can protect against rotenoneinduced neurotoxicity to ameliorate motor deficits, which may be mediated through activating AhR pathway. K E Y W O R D Saromatic hydrocarbon receptor pathway, dietary tryptophan, Parkinson's disease INTRODUCTIONParkinson's disease (PD) is the second most common neurodegenerative disease, and is increasingly receiving attention from multipleThis is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

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“…The diagnosis of sepsis and septic shock was defined in accordance with the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) 25 . The septic patients and healthy controls who met the exclusion criteria were excluded according to our previous studies 3 , 26 . The clinical variables such as gender, age, blood microbiological cultures, source of infection, Sequential Organ Failure Assessment (SOFA) and APACHE II score were collected.…”

Section: Methodsmentioning

confidence: 99%

A gain-of-function NLRP3 3′-UTR polymorphism causes miR-146a-mediated suppression of NLRP3 expression and confers protection against sepsis progression

Chen²,

Hong

et al. 2021

Sci Rep

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Nucleotide-binding domain and leucine-rich repeat (LRR)-containing family protein 3 (NLRP3) regulated the maturation of inflammation-related cytokines by forming NLRP3 inflammasome, which plays pivotal roles in sepsis pathogenesis. In this study, we evaluated the genetic association of NLRP3 polymorphisms with sepsis (640 patients and 769 controls) and characterized the impact of NLRP3 polymorphisms on NLRP3 expression and inflammatory responses. No significant differences were observed in genotype/allelic frequencies of NLRP3 29940G>C between sepsis cases and controls. The G allele was significantly overrepresented in patients with septic shock than those in sepsis subgroup, and the GC/GG genetypes were related to the 28-day mortality of sepsis. Lipopolysaccharide challenge to peripheral blood mononuclear cells showed a significant suppression of NLRP3 mRNA expression and release of IL-1β and TNF-α in CC compared with the GC/GG genotype category. Functional experiments with luciferase reporter vectors containing the NLRP3 3′-UTR with the 29940 G-to-C variation in HUVECs and THP-1 cells showed a potential suppressive effect of miR-146a on NLRP3 transcription in the presence of the C allele. Taken together, these results demonstrated that the 29940 G-to-C mutation within the NLRP3 3′-UTR was a gain-of-function alteration that caused the suppression of NLRP3 expression and downstream inflammatory cytokine production via binding with miR-146a, which ultimately protected patients against susceptibility to sepsis progression and poor clinical outcome.

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Tryptophan Metabolism Activates Aryl Hydrocarbon Receptor-Mediated Pathway To Promote HIV-1 Infection and Reactivation

Cited by 29 publications

References 81 publications

The Aryl Hydrocarbon Receptor as a Modulator of Anti-viral Immunity

The Aryl Hydrocarbon Receptor as a Modulator of Anti-viral Immunity

Tryptophan in the diet ameliorates motor deficits in a rotenone‐induced rat Parkinson's disease model via activating the aromatic hydrocarbon receptor pathway

A gain-of-function NLRP3 3′-UTR polymorphism causes miR-146a-mediated suppression of NLRP3 expression and confers protection against sepsis progression

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