[Inhibitory Effects of Dabigatran on Airway Inflammation Induced by Lipopolysaccharide in Mice].
Yakugaku Zasshi
; 140(12): 1477-1483, 2020 Dec 01.
Article
em Ja
| MEDLINE
| ID: mdl-32921648
ABSTRACT
Asthma and chronic obstructive pulmonary disease (COPD) are characterised by chronic inflammation in the lung that is associated with airway obstruction. Inhaled therapy with a combination of corticosteroid and a long-acting ß2-agonist is an effective anti-inflammatory medicine for asthma, but in patients with severe asthma and COPD fails to completely control these symptoms with current therapies. The inflammatory process in these diseases, which involves activation of the coagulation and fibrinolytic system in the lung, offers the opportunity for alternative anti-inflammatory therapies. In this study, we investigated the effects of anti-coagulants on lipopolysaccharide (LPS)-induced airway inflammation in mice. A/J mice were exposed to LPS, a bacterial endotoxin, intranasally and accumulation of inflammatory cells, TNF-α, C-X-C motif chemokine (CXCL) 1, and osteopontin in bronchoalveolar lavage fluid (BALF) was monitored by flow cytometry and an enzyme-linked immunosorbent assay. LPS exposure induced airway neutrophilia and accumulation of TNF-α, CXCL1, and osteopontin in BALF. This LPS-induced airway inflammation was not relieved using a corticosteroid, fluticasone propionate (FP), or a direct inhibitor of Factor Xa, rivaroxaban. In contrast, a direct thrombin inhibitor, dabigatran, inhibited LPS-induced airway neutrophilia and decreased inflammatory cytokine production in a dose dependent manner. Furthermore, combination of dabigatran and FP elicited stronger inhibition of LPS-induced airway inflammation. Therefore, these results suggest that dabigatran could be an effective new therapy for severe respiratory diseases.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Asma
/
Antitrombinas
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Lipopolissacarídeos
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Doença Pulmonar Obstrutiva Crônica
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Dabigatrana
Tipo de estudo:
Diagnostic_studies
/
Prognostic_studies
Limite:
Animals
Idioma:
Ja
Revista:
Yakugaku Zasshi
Ano de publicação:
2020
Tipo de documento:
Article