Casapse-1 is not required for the induction of Silica-induced autoimmunity

Autor: Rahul D. Pawar, Jessica Mayeux, Timothy Cooper, Alaa S. Awad, Dwight H Kono, Kenneth M. Pollard
Rok vydání: 2016
Předmět:
Zdroj: The Journal of Immunology. 196:48.18-48.18
ISSN: 1550-6606
0022-1767
DOI: 10.4049/jimmunol.196.supp.48.18
Popis: Occupational exposure to respirable crystalline silica induces silicosis in humans & has been associated with lupus (SLE), but the specific mechanisms & susceptibility factors are largely unknown. Recent studies have highlighted a prominent role for interleukin-1β in silica-induced lung inflammation. Caspase-1 is predominantly involved in the cleavage of pro-IL-1β to active IL-1β. Therefore, we investigated the role of IL-1β in the severity of lung damage & autoimmune response to silica by exposing B10.S and Caspase-1 deficient B10.S (B10.S-Casp1−/−) mice to crystalline silica (1 mg in 25 μl) in PBS or PBS only, by intranasal instillation twice a week for 4 weeks. When analyzed for autoimmunity at 28 weeks post-exposure, both B10.S and B10.S-Casp1−/− mice developed similar elevated levels of anti-chromatin & anti-nuclear antibodies in serum & broncho-alveolar lavage (BAL) compared to PBS controls. Correspondingly, both silica-treated B10.S and B10.S-Casp1−/−mice had a significant peribronchial & perivascular lymphocytic infiltrates (PLI), alveolar proteinosis (AP), and alveolitis, but the PLI and AP were significantly higher in B10.S mice than B10.S-Casp1−/−mice. Similarly, robust increases in the levels of total protein & cell numbers in BAL fluid, but total protein was significantly higher in B10.S mice than B10.S-Casp1−/−mice. Higher numbers of inflammatory M1 macrophages (CD11b+Ly6chi) & neutrophils (Ly6Ghi) were also observed in both groups of silica-treated mice. These findings indicate that caspase-1 and by inference IL-1β is not required for silica-induced autoimmunity in mice, but contributes to the lung inflammation, & suggests that NLRP3 inflammasome, cathepsin C, elastase, granzyme B may be more important.
Databáze: OpenAIRE
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