Inhibitions of HMGB1 and TLR4 alleviate DINP-induced asthma in mice
Inhibitions of HMGB1 and TLR4 alleviate DINP-induced asthma in mice
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DOI：
10.1039/c9tx00048h
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发表时间：
2019-09-01
影响因子：
2.1
通讯作者：
Yee, Sung-Tae
中科院分区：
文献类型：
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作者：
Hwang, Yun-Ho;Lee, Yongjin;Yee, Sung-Tae
我们研究了高迁移率族蛋白1（HMGB1）和TLR4在邻苯二甲酸二异壬酯（DINP）诱导的哮喘中的作用。用TLR4信号传导抑制剂或抗HMGB1抗体处理DINP诱导哮喘的小鼠，24小时后测量各种哮喘标志物。DINP增加气道高反应性、BALF中的细胞数量、血液中的炎性细胞（白细胞、淋巴细胞、单核细胞、嗜酸性粒细胞、中性粒细胞、嗜碱性粒细胞）数量、粘液生成、肺纤维化、BALF中的Th2型细胞因子水平和肺细胞凋亡。另一方面，对DINP诱导的哮喘小鼠模型给予TLR4信号传导抑制剂（TAK-242）或抗HMGB1抗体可减少哮喘的生物标志物。这些结果表明，TLR4和HMGB1均有助于DINP诱导的哮喘，并且TLR4或HMGB1的抑制提供了治疗邻苯二甲酸酯（如DINP）诱导的哮喘的潜在方法。
We studied the effects of high mobility group box chromosomal protein 1 (HMGB1) and toll-like receptor (TLR4) in diisonoyl phthalate (DINP)-induced asthma. Mice with DINP-induced asthma were treated with a TLR4-signaling inhibitor or anti-HMGB1 antibody, and various markers of asthma were measured 24 h later. DINP increased airway hyperresponsiveness, numbers of cells in BALF, numbers of inflammatory cells (leukocytes, lymphocytes, monocytes, eosinophils, neutrophils, basophils) in blood, mucus production, pulmonary fibrosis, Th2 type cytokine levels in BALF, and lung cell apoptosis. On the other hand, administrations of TLR4-signaling inhibitors (TAK-242) or anti-HMGB1 antibodies to a mouse model of DINP-induced asthma reduced biological markers of asthma. These results show TLR4 and HMGB1 both contribute to DINP-induced asthma, and that the inhibitions of TLR4 or HMGB1 offer potential means of treating asthma induced by phthalates like DINP.