MEXT Innovative Research Center for Preventive Medical Engineering, Nagoya University, Furou-cho, Chikusa-ku, Nagoya, 464-8603, Japan.
Inflamm Res. 2009 Oct;58(10):705-15. doi: 10.1007/s00011-009-0039-1. Epub 2009 Apr 24.
We investigated the involvement of heme oxygenase (HO)-1 in the anti-allergic action of quercetin against degranulation of rat basophilic leukemia (RBL-2H3) cells, rat peritoneal mast cells, and mouse bone marrow-derived mast cells.
The strength of allergic reaction was evaluated by the extent of degranulation in mast cells sensitized with various stimulants. The levels of HO-1, HO-2, and nuclear factor erythroid 2-related factor 2 (Nrf2) expressions were determined by quantitative RT-PCR, western blotting, or immunocytochemistry.
Heme oxygenase activity was upregulated after short exposure to quercetin, followed by the induction of HO-1 expression after long exposure to quercetin. The inhibition of degranulation by quercetin was reversed using tin protoporphyrin IX (SnPP), an HO-1 inhibitor. HO-1 metabolites, bilirubin and CO, led to inhibit degranulation, and quercetin translocated Nrf2 from cytoplasm into nucleus in RBL-2H3 cells.
These results strongly suggest that quercetin exerted anti-allergic actions via activation of Nrf2-HO-1 pathway.
我们研究了血红素加氧酶（HO）-1 是否参与槲皮素对大鼠嗜碱性白血病（RBL-2H3）细胞、大鼠腹腔肥大细胞和小鼠骨髓来源肥大细胞脱颗粒的抗过敏作用。
通过用各种刺激物敏化的肥大细胞的脱颗粒程度来评估过敏反应的强度。通过定量 RT-PCR、western blot 或免疫细胞化学测定 HO-1、HO-2 和核因子红细胞 2 相关因子 2（Nrf2）的表达水平。
短时间暴露于槲皮素后血红素加氧酶活性上调，长时间暴露于槲皮素后诱导 HO-1 表达。HO-1 抑制剂锡原卟啉 IX（SnPP）逆转了槲皮素对脱颗粒的抑制作用。HO-1 代谢物胆红素和 CO 导致脱颗粒抑制，槲皮素将 Nrf2 从细胞质转位到细胞核内。
这些结果强烈表明，槲皮素通过激活 Nrf2-HO-1 通路发挥抗过敏作用。
