Leukotriene C4 aggravates bleomycin-induced pulmonary fibrosis in mice.
Respirology
; 18(4): 674-81, 2013 May.
Article
em En
| MEDLINE
| ID: mdl-23432979
ABSTRACT
BACKGROUND AND OBJECTIVE:
Synthesis of cysteinyl leukotrienes (cys-LT) is thought to cause inflammatory disorders such as bronchial asthma and allergic rhinitis. Recent reports have suggested that leukotriene C4 (LTC4 ) is an important regulator of pulmonary fibrosis. This study examined the effect of LTC4 in LTC4 synthase-overexpressed transgenic mice with bleomycin-induced pulmonary fibrosis. The function of lung-derived fibroblasts from transgenic mice was also investigated.METHODS:
Bleomycin was administrated to transgenic mice and wild-type (WT) mice by intratracheal instillation. Concentrations of interleukin (IL)-4 and -13, interferon-γ, and transforming growth factor (TGF)-ß1 in bronchoalveolar lavage fluid were measured 1, 3, 7 and 14 days after the administration of bleomycin. Lung tissue was examined histopathologically on day 14. In addition, lung-derived fibroblasts from transgenic and WT mice were cultured for 7 days. Expression of TGF-ß1 mRNA was measured by real-time polymerase chain reaction.RESULTS:
Both the pathological scores for pulmonary fibrosis (3.8 ± 0.4 vs 2.0 ± 0.1, P < 0.05) and the levels of IL-4 (12.1 ± 2.3 vs <7.8 pg/mL, P < 0.05), IL-13 (26.5 ± 5.2 vs <7.8 pg/mL, P < 0.01) and TGF-ß1 (211.1 ± 30.2 vs 21.3 ± 1.2 pg/mL, P < 0.01) on day 14 were significantly greater in transgenic than in WT mice. Furthermore, the reduction of LTC4 by pranlukast hydrate, a cys-LT1 receptor antagonist, in fibroblasts from transgenic significantly (P < 0.05) decreased the expression of TGF-ß1 mRNA (by â¼50%) compared with those from WT mice.CONCLUSIONS:
Overexpression of LTC4 , amplifies bleomycin-induced pulmonary fibrosis in mice. Our findings suggest a role for LTC4 in lung fibrosis.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Fibrose Pulmonar
/
Bleomicina
/
Leucotrieno C4
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article