A further investigation concerning correlation between anti-fibrotic effect of liposomal quercetin and inflammatory cytokines in pulmonary fibrosis.
It is widely accepted that inflammatory cells and cytokines play vital roles in the process of pulmonary fibrosis. The aim of this study was to evaluate the preventative effects of liposomal quercetin against bleomycin-induced pulmonary fibrosis in vivo. The underlying molecular mechanisms were also investigated. Bleomycin was injected intratracheally at a single dose of 5 U/kg for pulmonary fibrosis induction. Liposomal quercetin was intravenously injected 1 day prior to bleomycin administration and continued to the end of the study (for 4 weeks). Our results showed that liposomal quercetin diminished the increase of total cell counts and macrophage counts in bronchoalveolar lavage fluid. The neutrophil and lymphocyte counts were also significantly decreased both on day 7 and 14 after liposomal quercetin injection (P<0.05). The levels of TNF-alpha, IL-1beta, and IL-6 in bronchoalveolar lavage fluid at day 7 were strikingly reduced in liposomal quercetin treated group compared with bleomycin-induced group (TNF-alpha: 56.21+/-3.16 pg/ml vs.79.85+/-6.91 pg/ml; IL-1beta: 37.64+/-2.10 pg/ml vs. 73.29+/-5.78 pg/ml; IL-6: 88.52+/-5.96 pg/ml vs. 128.56+/-8.72 pg/ml; P<0.05). Moreover, the treatment with liposomal quercetin exerted approximately 35.8% reduction of the hydroxyproline content in contrast to the bleomycin-induced group (P<0.05). Histopathological assessment revealed that treatment with liposomal quercetin apparently lessened the lung fibrosis areas and collagen deposition accompanied with decreased expression of TGF-beta1. Thus, our results suggested that liposomal quercetin could attenuate the bleomycin-induced pulmonary fibrosis in vivo by the suppression of inflammatory cytokines.
State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, China.
Qi
Q
Baowen
Zhao
Z
Yulin
Wei
W
Xin
Xiao
X
Wenjing
Zheng
Z
Hao
Chen
C
Zhizhi
Duan
D
Xingmei
Zhao
Z
Xia
Wei
W
Yuquan
Chen
C
Lijuan
D000818:Animals; D001761:Bleomycin / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D006909:Hydroxyproline / Q000378:metabolism; D007249:Inflammation / Q000378:metabolism; D008081:Liposomes; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D011014:Pneumonia / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D011794:Quercetin / Q000008:administration & dosage* / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
D016207:Cytokines; D008081:Liposomes; D053773:Transforming Growth Factor beta1; D001761:Bleomycin; D011794:Quercetin; D006909:Hydroxyproline