Tetracycline ameliorates silica-induced pulmonary inflammation and fibrosis via inhibition of caspase-1.
Anti-bacterial agents
Immunomodulation
Inflammasomes
Lung injury
NLR Proteins
Pyroptosis
Silicon dioxide
Silicosis
Journal
Respiratory research
ISSN: 1465-993X
Titre abrégé: Respir Res
Pays: England
ID NLM: 101090633
Informations de publication
Date de publication:
07 Feb 2022
07 Feb 2022
Historique:
received:
29
07
2021
accepted:
20
01
2022
entrez:
8
2
2022
pubmed:
9
2
2022
medline:
22
3
2022
Statut:
epublish
Résumé
Inhalation of dust containing silica particles is associated with severe pulmonary inflammation and lung injury leading to chronic silicosis including fibrotic remodeling of the lung. Silicosis represents a major global health problem causing more than 45.000 deaths per year. The inflammasome-caspase-1 pathway contributes to the development of silica-induced inflammation and fibrosis via IL-1β and IL-18 production. Recent studies indicate that tetracycline can be used to treat inflammatory diseases mediated by IL-1β and IL-18. Therefore, we hypothesized that tetracycline reduces silica-induced lung injury and lung fibrosis resulting from chronic silicosis via limiting IL-1β and IL-18 driven inflammation. To investigate whether tetracycline is a therapeutic option to block inflammasome-caspase-1 driven inflammation in silicosis, we incubated macrophages with silica alone or combined with tetracycline. The in vivo effect of tetracycline was determined after intratracheal administration of silica into the mouse lung. Tetracycline selectively blocks IL-1β production and pyroptotic cell death via inhibition of caspase-1 in macrophages exposed to silica particles. Consistent, treatment of silica-instilled mice with tetracycline significantly reduced pulmonary caspase-1 activation as well as IL-1β and IL-18 production, thereby ameliorating pulmonary inflammation and lung injury. Furthermore, prolonged tetracycline administration in a model of chronic silicosis reduced lung damage and fibrotic remodeling. These findings suggest that tetracycline inhibits caspase-1-dependent production of IL-1β in response to silica in vitro and in vivo. The results were consistent with tetracycline reducing silica-induced pulmonary inflammation and chronic silicosis in terms of lung injury and fibrosis. Thus, tetracycline could be effective in the treatment of patients with silicosis as well as other diseases involving silicotic inflammation.
Sections du résumé
BACKGROUND
BACKGROUND
Inhalation of dust containing silica particles is associated with severe pulmonary inflammation and lung injury leading to chronic silicosis including fibrotic remodeling of the lung. Silicosis represents a major global health problem causing more than 45.000 deaths per year. The inflammasome-caspase-1 pathway contributes to the development of silica-induced inflammation and fibrosis via IL-1β and IL-18 production. Recent studies indicate that tetracycline can be used to treat inflammatory diseases mediated by IL-1β and IL-18. Therefore, we hypothesized that tetracycline reduces silica-induced lung injury and lung fibrosis resulting from chronic silicosis via limiting IL-1β and IL-18 driven inflammation.
METHODS
METHODS
To investigate whether tetracycline is a therapeutic option to block inflammasome-caspase-1 driven inflammation in silicosis, we incubated macrophages with silica alone or combined with tetracycline. The in vivo effect of tetracycline was determined after intratracheal administration of silica into the mouse lung.
RESULTS
RESULTS
Tetracycline selectively blocks IL-1β production and pyroptotic cell death via inhibition of caspase-1 in macrophages exposed to silica particles. Consistent, treatment of silica-instilled mice with tetracycline significantly reduced pulmonary caspase-1 activation as well as IL-1β and IL-18 production, thereby ameliorating pulmonary inflammation and lung injury. Furthermore, prolonged tetracycline administration in a model of chronic silicosis reduced lung damage and fibrotic remodeling.
CONCLUSIONS
CONCLUSIONS
These findings suggest that tetracycline inhibits caspase-1-dependent production of IL-1β in response to silica in vitro and in vivo. The results were consistent with tetracycline reducing silica-induced pulmonary inflammation and chronic silicosis in terms of lung injury and fibrosis. Thus, tetracycline could be effective in the treatment of patients with silicosis as well as other diseases involving silicotic inflammation.
Identifiants
pubmed: 35130879
doi: 10.1186/s12931-022-01937-7
pii: 10.1186/s12931-022-01937-7
pmc: PMC8822850
doi:
Substances chimiques
Caspase Inhibitors
0
Protein Synthesis Inhibitors
0
Silicon Dioxide
7631-86-9
Caspase 1
EC 3.4.22.36
Tetracycline
F8VB5M810T
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
21Informations de copyright
© 2022. The Author(s).
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