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- Title
IL-37 Inhibits Inflammasome Activation and Disease Severity in Murine Aspergillosis.
- Authors
Moretti, Silvia; Bozza, Silvia; Oikonomou, Vasilis; Renga, Giorgia; Casagrande, Andrea; Iannitti, Rossana G.; Puccetti, Matteo; Garlanda, Cecilia; Kim, Soohyun; Li, Suzhao; van de Veerdonk, Frank L.; Dinarello, Charles A.; Romani, Luigina
- Abstract
Since IL-37 transgenic mice possesses broad anti-inflammatory properties, we assessed whether recombinant IL-37 affects inflammation in a murine model of invasive pulmonary aspergillosis. Recombinant human IL-37 was injected intraperitoneally into mice prior to infection and the effects on lung inflammation and inflammasome activation were evaluated. IL-37 markedly reduced NLRP3-dependent neutrophil recruitment and steady state mRNA levels of IL-1β production and mitigated lung inflammation and damage in a relevant clinical model, namely aspergillosis in mice with cystic fibrosis. The anti-inflammatory activity of IL-37 requires the IL-1 family decoy receptor TIR-8/SIGIRR. Thus, by preventing activation of the NLRP3 inflammasome and reducing IL-1β secretion, IL-37 functions as a broad spectrum inhibitor of the innate response to infection-mediated inflammation, and could be considered to be therapeutic in reducing the pulmonary damage due to non-resolving Aspergillus infection and disease.
- Subjects
INTERLEUKIN-33; PNEUMONIA; MESSENGER RNA; INFLAMMATION; TRANSGENIC mice
- Publication
PLoS Pathogens, 2014, Vol 10, Issue 11, p1
- ISSN
1553-7366
- Publication type
Article
- DOI
10.1371/journal.ppat.1004462