Protective effects of intratracheally administered quercetin on lipopolysaccharide-induced acute lung injury

Respiratory Research

Tsutomu Kawabe¹  Yoshinori Hasegawa²  Naozumi Hashimoto²  Mitsuo Sato²  Haruka Nose¹  Katsunori Hashimoto¹  Miyoko Matsushima¹  Koji Takashima² 

[1] Department of Pathophysiological Laboratory Sciences, Nagoya University Graduate School of Medicine, 1-1-20 Daikou-minami, Higashi-ku 461-8673, Nagoya, Japan;Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan

关键词: Acute lung injury;    Alveolar macrophage;    Intratracheal administration;    Heme oxygenase 1;    Quercetin;   

Others  :  1137238
DOI  :  10.1186/s12931-014-0150-x

 received in 2014-08-26, accepted in 2014-11-11,  发布年份 2014

【 摘 要 】

Background

Acute respiratory distress syndrome (ARDS) can result in a life-threatening form of respiratory failure, and established, effective pharmacotherapies are therefore urgently required. Quercetin is one of the most common flavonoids found in fruits and vegetables, and has potent anti-inflammatory and anti-oxidant activities. Quercetin has been demonstrated to exhibit cytoprotective effects through the induction of heme oxygenase (HO)-1. Here, we investigated whether the intratracheal administration of quercetin could suppress lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice as well as the involvement of HO-1 in quercetin’s suppressive effects.

Methods

Mouse model of ALI were established by challenging intratracheally LPS. The wet lung-to-body weight ratio, matrix metalloproteinase (MMP)-9 activities, and pro-inflammatory cytokine productions, including tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 in bronchoalveolar lavage fluid (BALF) were examined in ALI mice with or without quercetin pretreatment. We also examined the effects of quercetin on LPS stimulation in the mouse alveolar macrophage cell line, AMJ2-C11 cells.

Results

Intratracheal administration of quercetin decreased the wet lung-to-body weight ratio. Moreover, quercetin decreased MMP-9 activity and the production of pro-inflammatory cytokines in BALF cells activated by LPS in advance. We determined the expression of quercetin-induced HO-1 in mouse lung, e.g., alveolar macrophages (AMs), alveolar and bronchial epithelial cells. When AMJ2-C11 cells were cultured with quercetin, a marked suppression of LPS-induced pro-inflammatory cytokine production was observed. The cytoprotective effects were attenuated by the addition of the HO-1 inhibitor SnPP. These results indicated that quercetin suppressed LPS-induced lung inflammation, and that an HO-1-dependent pathway mediated these cytoprotective effects.

Conclusions

Our findings indicated that quercetin suppressed LPS-induced lung inflammation, and that an HO-1-dependent pathway mediated these cytoprotective effects. Intratracheal administration of quercetin will lead to new supportive strategies for cytoprotection in these serious lung conditions.

【 授权许可】

   
2014 Takashima et al.; licensee BioMed Central.

【 图 表 】

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