Aryl hydrocarbon receptor negatively regulates NLRP3 inflammasome activity by inhibiting NLRP3 transcription

Huai, Wanwan; Zhao, Rui; Song, Hui; Zhao, Jing; Zhang, Lei; Zhang, Lining; Gao, Chengjiang; Han, Lihui; Zhao, Wei

doi:10.1038/ncomms5738

Cited by 173 publications

(158 citation statements)

References 52 publications

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“…107 The aryl hydrocarbon receptor (AhR) negatively regulates NLRP3-mediated caspase-1 activation and IL-1b secretion in macrophages through binding to the xenobiotic response element in the NLRP3 promoter and inhibiting NLRP3 transcription. 125 Another recent study showed that IkB kinase a (IKKa) is a negative regulator of ASC-dependent inflammasome activation through interaction with the inflammasome adaptor ASC. 126 Signal 2 activation of the NLRP3 inflammasome attenuates the kinase activity of IKKa through recruitment of phosphatase PP2A, thus releasing ASC to participate in inflammasome assembly.…”

Section: Negative Regulation Of Nlrp3 Inflammasome Complex Activationmentioning

confidence: 99%

Molecular mechanisms regulating NLRP3 inflammasome activation

et al. 2015

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Section: Negative Regulation Of Nlrp3 Inflammasome Complex Activationmentioning

confidence: 99%

Molecular mechanisms regulating NLRP3 inflammasome activation

et al. 2015

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“…Luciferase activities were measured with Dual-Luciferase Reporter Assay System (Promega), according to the manufacturer's instructions (24,25). Data are normalized for transfection efficiency by subtracting Firefly luciferase activity with that of Renilla luciferase.…”

Section: Luciferase Assaymentioning

confidence: 99%

“…For Western blot, cells were lysed with M-PER Protein Extraction Reagent (Pierce, Rockford, IL) supplemented with a protease inhibitor "mixture," and then protein concentrations in the extracts were measured with a bicinchoninic acid assay (Pierce). Equal amounts of extracts were separated by SDS-PAGE and then were transferred onto nitrocellulose membranes for immunoblot analysis (24,25).…”

Section: Immunoprecipitation and Western Blotmentioning

confidence: 99%

“…HEK293-TLR3 and HEK293-TLR4 cell lines were obtained from InvivoGen. The cells were cultured at 37˚C under 5% CO 2 in DMEM supplemented with 10% FCS (Invitrogen Life Technologies), 100 U/ml penicillin, and 100 mg/ml streptomycin (24,25).…”

Section: Cell Culturementioning

confidence: 99%

“…For stable selection of RAW264.7 cell lines overexpressing PTPN4, transfected RAW264.7 macrophages were selected with G418 (800 mg/ml) and pooled for further experiments (24,25). For transient silencing, duplexes of small interfering RNA (siRNA) were transfected into cells with the Geneporter 2 Transfection Reagent (GTS, San Diego, CA), according to the standard protocol (23,24). Target sequences for transient silencing were 59-GGAUUUGUUAAACCAUUAA-39 (siRNA 1) and 59-GGUUUGGAUUC-AAUGUAAA-39 (siRNA 2) for PTPN4, and "scrambled" control sequences were 59-UUCUCCGAACGUGUCACGU-39.…”

Section: Transfectionmentioning

confidence: 99%

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Phosphatase PTPN4 Preferentially Inhibits TRIF-Dependent TLR4 Pathway by Dephosphorylating TRAM

Huai

Song

Wang

et al. 2015

The Journal of Immunology

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TLR4 recruits TRIF-related adaptor molecule (TRAM, also known as TICAM2) as a sorting adaptor to facilitate the interaction between TLR4 and TRIF and then initiate TRIF-dependent IRF3 activation. However, the mechanisms by which TRAM links downstream molecules are not fully elucidated. In this study, we show that TRAM undergoes tyrosine phosphorylation upon TLR4 activation and that is required for TLR4-induced IRF3 activation. Protein tyrosine phosphatase nonreceptor type 4 (PTPN4), a protein tyrosine phosphatase, inhibits tyrosine phosphorylation and subsequent cytoplasm translocation of TRAM, resulting in the disturbance of TRAM–TRIF interaction. Consequently, PTPN4 specifically inhibits TRIF-dependent IRF3 activation and IFN-β production in TLR4 pathway. Therefore, our results provide new insight into the TLR4 pathway and identify PTPN4 as a specific inhibitor of TRIF-dependent TLR4 pathway. Targeting PTPN4 would be beneficial for the development of new strategy to control TLR4-associated diseases without unwanted side effects.

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Blautia Coccoides is a Newly Identified Bacterium Increased by Leucine Deprivation and has a Novel Function in Improving Metabolic Disorders

Niu,

Hu,

Song

et al. 2024

Advanced Science

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Gut microbiota is linked to human metabolic diseases. The previous work showed that leucine deprivation improved metabolic dysfunction, but whether leucine deprivation alters certain specific species of bacterium that brings these benefits remains unclear. Here, this work finds that leucine deprivation alters gut microbiota composition, which is sufficient and necessary for the metabolic improvements induced by leucine deprivation. Among all the affected bacteria, B. coccoides is markedly increased in the feces of leucine‐deprived mice. Moreover, gavage with B. coccoides improves insulin sensitivity and reduces body fat in high‐fat diet (HFD) mice, and singly colonization of B. coccoides increases insulin sensitivity in gnotobiotic mice. The effects of B. coccoides are mediated by metabolizing tryptophan into indole‐3‐acetic acid (I3AA) that activates the aryl hydrocarbon receptor (AhR) in the liver. Finally, this work reveals that reduced fecal B. coccoides and I3AA levels are associated with the clinical metabolic syndrome. These findings suggest that B. coccoides is a newly identified bacterium increased by leucine deprivation, which improves metabolic disorders via metabolizing tryptophan into I3AA.

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Aryl hydrocarbon receptor negatively regulates NLRP3 inflammasome activity by inhibiting NLRP3 transcription

Cited by 173 publications

References 52 publications

Molecular mechanisms regulating NLRP3 inflammasome activation

Molecular mechanisms regulating NLRP3 inflammasome activation

Phosphatase PTPN4 Preferentially Inhibits TRIF-Dependent TLR4 Pathway by Dephosphorylating TRAM

Blautia Coccoides is a Newly Identified Bacterium Increased by Leucine Deprivation and has a Novel Function in Improving Metabolic Disorders

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