دورية أكاديمية
NLRP3 at the crossroads between immune/inflammatory responses and enteric neuroplastic remodelling in a mouse model of diet-induced obesity
| العنوان: | NLRP3 at the crossroads between immune/inflammatory responses and enteric neuroplastic remodelling in a mouse model of diet-induced obesity |
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| المؤلفون: | Pelegrini, Carolina, Fornai, Matteo, Benvenuti, Laura, Palazon-Riquelme, Pablo, Giron, Maria Cecilia, Nericcio, Ana, Garelli, Francesca, D'Antongiovanni,, Vanessa, Segnani, Cristina, Ipolito, Chiara, Nannipieri, Monica, Lopez-Castejon, Gloria, Pelegrin, Pablo, Hasko, György, Bernardini, Nunzia, Blandizi, Corrado, Antonioli, Luca |
| المصدر: | Pelegrini , C , Fornai , M , Benvenuti , L , Palazon-Riquelme , P , Giron , M C , Nericcio , A , Garelli , F , D'Antongiovanni, V , Segnani , C , Ipolito , C , Nannipieri , M , Lopez-Castejon , G , Pelegrin , P , Hasko , G , Bernardini , N , Blandizi , C & Antonioli , L 2021 , ' NLRP3 at the crossroads between immune/inflammatory responses and enteric neuroplastic remodelling in a mouse model of diet-induced obesity ' , British Journal of Pharmacology , vol. 178 , no. .... |
| سنة النشر: | 2021 |
| المجموعة: | The University of Manchester: Research Explorer - Publications |
| مصطلحات موضوعية: | NLRP3 inflammasome, colonic motility, high-fat diet, inflammation, macrophages, obesity, substance P, tachykinin neurotransmission |
| الوصف: | Background and Purpose: Enteric neurogenic/inflammation contributes to bowel dysmotility in obesity. We examined the role of NLRP3 in colonic neuromuscular dysfunctions in mice with high-fat diet (HFD)-induced obesity. Experimental Approach: Wild-type C57BL/6J and NLRP3-KO (Nlrp3 −/− ) mice were fed with HFD or standard diet for 8 weeks. The activation of inflammasome pathways in colonic tissues from obese mice was assessed. The role of NLRP3 in in vivo colonic transit and in vitro tachykininergic contractions and substance P distribution was evaluated. The effect of substance P on NLRP3 signalling was tested in cultured cells. Key Results: HFD mice displayed increased body and epididymal fat weight, cholesterol levels, plasma resistin levels and plasma and colonic IL-1β levels, colonic inflammasome adaptor protein apoptosis-associated speck-like protein containing caspase-recruitment domain (ASC) and caspase-1 mRNA expression and ASC immunopositivity in macrophages. Colonic tachykininergic contractions were enhanced in HFD mice. HFD NLRP3 −/− mice developed lower increase in body and epididymal fat weight, cholesterol levels, systemic and bowel inflammation. In HFD Nlrp3 −/− mice, the functional alterations of tachykinergic pathways and faecal output were normalized. In THP-1 cells, substance P promoted IL-1β release. This effect was inhibited upon incubation with caspase-1 inhibitor or NK 1 antagonist and not observed in ASC −/− cells. Conclusion and Implications: In obesity, NLRP3 regulates an interplay between the shaping of enteric immune/inflammatory responses and the activation of substance P/NK 1 pathways underlying the onset of colonic dysmotility. Identifying NLRP3 as a therapeutic target for the treatment of bowel symptoms related to obesity. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| DOI: | 10.1111/bph.15532 |
| الإتاحة: | https://doi.org/10.1111/bph.15532Test https://research.manchester.ac.uk/en/publications/f86d96c7-0b38-4b43-95e4-0396f59698fcTest https://pure.manchester.ac.uk/ws/files/204611309/bph.15532.pdfTest |
| حقوق: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.3F15D93B |
| قاعدة البيانات: | BASE |
| DOI: | 10.1111/bph.15532 |
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