Induction of heme oxygenas-1 attenuates NLRP3 inflammasome activation in lipopolysaccharide-induced mastitis in mice
Induction of heme oxygenas-1 attenuates NLRP3 inflammasome activation in lipopolysaccharide-induced mastitis in mice
复制标题
诱导血红素 Oxyas-1 减弱脂多糖诱导的小鼠乳腺炎中 NLRP3 炎症小体的激活
DOI：
10.1016/j.intimp.2017.09.007
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发表时间：
2017-11-01
影响因子：
5.6
通讯作者：
Zhang, Naisheng
中科院分区：
文献类型：
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作者：
Hu Xiaoyu;Si, Hongbin;Zhang, Naisheng
乳腺炎是世界范围内奶牛生产中最常见的疾病之一，给奶牛生产造成了巨大的经济损失。血红素氧合酶-1（HO-1）是一种细胞保护酶，参与氧化应激反应和炎症反应。本研究旨在探讨HO-1对LPS诱导的小鼠乳腺炎的保护作用。BALB/c小鼠在LPS刺激前2 h用血红素（HO-1诱导剂）和锌原卟啉（ZnPP; HO-1抑制剂）预处理。结果表明，与单纯LPS刺激组相比，氯化血红素预处理组乳腺损伤程度、炎症细胞因子IL-1 β的产生及乳腺组织MPO活性均显著降低。然而，ZnPP逆转氯化血红素的作用。此外，我们发现，在LPS刺激后，ROS和NLRP 3炎性体的水平增加。氯化高铁血红素可抑制这种增加，ZnPP可阻断氯化高铁血红素对ROS产生和NLRP 3炎性体激活的抑制作用。此外，结果表明，氯化血红素减少硫氧还蛋白相互作用蛋白（TXNIP）的表达由LPS诱导，和ZnPP减弱这些变化。以上结果提示，HO-1的过度表达可能抑制了NLRP 3炎性体的激活和TXNIP的表达。HO-1的诱导表达有望成为一种抗LPS诱导乳腺炎的有效方法。
Mastitis is one of most prevalent production disease in dairy herds worldwide, and is responsible for enormous economic losses. Heme oxygenase-1 (HO-1) is a cytoprotective enzyme, which is involved in the response to oxidative stress and inflammatory response. The purpose of this study was to detect the protective effect of HO-1 on LPS-induced mastitis in mice. BALB/c mice were pretreated with hemin (HO-1 inducer) and zinc protoporphyrin (ZnPP; HO-1 inhibitor) at 2 h before LPS stimulation. The results showed that the mammary gland damage, production of inflammatory cytokines IL-1 beta, and MPO activity in mammary gland tissues were significantly reduced after pretreated with hemin compared with the group of LPS stimulation only. However, ZnPP reversed the effects of hemin. Furthermore, we found that the levels of ROS and NLRP3 inflammasome were increased after LPS stimulation. The increases were inhibited by hemin and the inhibition of hemin on ROS production and NLRP3 inflammasome activation were blocked by ZnPP. In addition, the results showed that hemin reduced the expression of thioredoxin-interacting protein (TXNIP) induced by LPS, and ZnPP attenuated these changes. In conclusion, the results suggested that overproduction of HO-1 may inhibit the activation of NLRP3 inflammasome and the expression of TXNIP. Induction of HO-1 may be served as a promising method against mastitis induced by LPS.