دورية أكاديمية
Inflammasome Activation in Ankylosing Spondylitis Is Associated With Gut Dysbiosis
| العنوان: | Inflammasome Activation in Ankylosing Spondylitis Is Associated With Gut Dysbiosis |
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| المؤلفون: | Guggino G., Mauro D., Rizzo A., Alessandro R., Raimondo S., Bergot A. -S., Rahman M. A., Ellis J. J., Milling S., Lories R., Elewaut D., Brown M. A., Thomas R., Ciccia F. |
| المساهمون: | Guggino G., Mauro D., Rizzo A., Alessandro R., Raimondo S., Bergot A.-S., Rahman M.A., Ellis J.J., Milling S., Lories R., Elewaut D., Brown M.A., Thomas R., Ciccia F. |
| بيانات النشر: | John Wiley and Sons Inc |
| سنة النشر: | 2021 |
| المجموعة: | IRIS Università degli Studi di Palermo |
| مصطلحات موضوعية: | Adolescent, Adult, Animals, Anti-Bacterial Agents, CARD Signaling Adaptor Proteins, Calcium-Binding Proteins, Case-Control Studies, Caspase 1, Crohn Disease, DNA-Binding Proteins, Dysbiosis, Female, Furans, Gastrointestinal Microbiome, HLA-B27 Antigen, Humans, Ileitis, Ileum, Immunohistochemistry, Indenes, Inflammasomes, Interleukin-17, Interleukin-18, Interleukin-1beta, Interleukin-23, Joints, Male, Mice, Middle Aged, NLR Family |
| الوصف: | Objective: We undertook this study to evaluate the activation and functional relevance of inflammasome pathways in ankylosing spondylitis (AS) patients and rodent models and their relationship to dysbiosis. Methods: An inflammasome pathway was evaluated in the gut and peripheral blood from 40 AS patients using quantitative reverse transcriptase–polymerase chain reaction (qRT-PCR), immunohistochemistry (IHC), flow cytometry, and confocal microscopy, and was compared to that of 20 healthy controls and 10 patients with Crohn’s disease. Bacteria was visualized using silver stain in human samples, and antibiotics were administered to HLA–B27–transgenic rats. The NLRP3 inhibitor MCC950 was administered to SKG mice, and ileal and joint tissues were assessed by IHC analysis and real-time qRT-PCR. The role of inflammasome in modulating the interleukin-23 (IL-23)/IL-17 axis was studied ex vivo. Results: Expression levels of Nlrp3, Nlrc4, and Aim2 were increased in the gut of HLA–B27–transgenic rats and reduced by antibiotic treatment (P < 0.05). In curdlan-treated SKG mice, NLRP3 blockade prevented ileitis and delayed arthritis onset (P < 0.05). Compared to healthy controls, AS patients demonstrated overexpression of NLRP3 (fold induction 2.33 versus 22.2; P < 0.001), NLRC4 (fold induction 1.90 versus 6.47; P < 0.001), AIM2 (fold induction 2.40 versus 20.8; P < 0.001), CASP1 (fold induction 2.53 versus 24.8; P < 0.001), IL1B (fold induction 1.07 versus 10.93; P<0.001), and IL18 (fold induction 2.56 versus 15.67; P < 0.001) in the ileum, and caspase 1 activity was increased (P<0.01). The score of adherent and invasive mucosa-associated bacteria was higher in AS (P < 0.01) and correlated with the expression of inflammasome components in peripheral blood mononuclear cells (P < 0.001).NLRP3expression was associated with disease activity (the Ankylosing Spondylitis Disease Activity Score using the C-reactive protein level) (r2 = 0.28, P < 0.01) andwith IL23A expression (r2 = 0.34, P < ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | info:eu-repo/semantics/altIdentifier/pmid/33452867; info:eu-repo/semantics/altIdentifier/wos/WOS:000653700600001; volume:73; issue:7; firstpage:1189; lastpage:1199; numberofpages:11; journal:ARTHRITIS & RHEUMATOLOGY; http://hdl.handle.net/10447/536449Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85106319063 |
| DOI: | 10.1002/art.41644 |
| الإتاحة: | https://doi.org/10.1002/art.41644Test http://hdl.handle.net/10447/536449Test |
| رقم الانضمام: | edsbas.F4E7AB09 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1002/art.41644 |
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