Boxb mediate BALB/c mice corneal inflammation through a TLR4/MyD88-dependent signaling pathway in Aspergillus fumigatus keratitis.
Boxb mediate BALB/c mice corneal inflammation through a TLR4/MyD88-dependent signaling pathway in Aspergillus fumigatus keratitis.
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DOI：
10.18240/ijo.2018.04.02
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发表时间：
2018-04
影响因子：
1.4
通讯作者：
Min Liu;Cui Li;Guiqiu Zhao;Jing Lin;Chengye Che;Qiang Xu;Qian Wang;Rui Xu;Yawen Niu
中科院分区：
文献类型：
--
作者：
Min Liu;Cui Li;Guiqiu Zhao;Jing Lin;Chengye Che;Qiang Xu;Qian Wang;Rui Xu;Yawen Niu
目的探讨高迁移率族蛋白1（HMGB 1）Boxb是否通过烟曲霉（Aspergillus fumigatus，A.烟曲霉）角膜炎。方法用磷酸盐缓冲液（PBS）、Boxb预处理小鼠角膜，A.烟曲霉感染腹腔巨噬细胞分别用PBS、Boxb、TLR 4抑制剂（CLI-095）、二甲基亚砜（DMSO）预处理。烟曲霉菌丝刺激。采用实时荧光定量逆转录聚合酶链反应（RT-PCR）检测HMGB 1在正常和感染小鼠角膜和巨噬细胞中的表达，Western blot和PCR检测TLR 4、MyD 88、白细胞介素1β（IL-1β）、肿瘤坏死因子α（TNF-α）的表达。结果A.烟曲霉感染而Boxb预处理组感染后TLR 4、HMGB 1、MyD 88、IL-1β、TNF-α的表达较PBS对照组显著增加。在BALB/c小鼠腹腔巨噬细胞中，Boxb预处理可增加TLR 4、HMGB 1、MyD 88、IL-1β、TNF-α的表达，而CLI-095和Boxb预处理可显著降低TLR 4、HMGB 1、MyD 88、IL-1β、TNF-α的表达。结论A. Boxb通过HMGB 1-TLR 4-MyD 88信号通路在角膜抗真菌免疫应答中发挥促炎作用。
AIM To investigate whether high-mobility group box 1 (HMGB1) Boxb exacerbates BALB/c mice corneal immune responses and inflammatory through the Toll-like receptor 4 (TLR4)/myeloid differentiation primary response 88 (MyD88)-dependent signaling pathway in Aspergillus fumigatus (A. fumigatus) keratitis. METHODS The mice corneas were pretreated with phosphate buffer saline (PBS), Boxb before A. fumigatus infection. The abdominal cavity extracted macrophages were pretreated with PBS, Boxb, TLR4 inhibitor (CLI-095), Dimethyl sulfoxide (DMSO) separately before A. fumigatus hyphae stimulation. HMGB1 was detected in normal and infected mice corneas and macrophages by real-time reverse transcriptase polymerase chain reaction (RT-PCR), the TLR4, MyD88, interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) were detected by Western blot and PCR. RESULTS In BALB/c mice corneas, the expressions of TLR4, HMGB1, IL-1β, TNF-α were increased after A. fumigatus infection. While pretreatment with Boxb significantly increased the expressions of TLR4, HMGB1, MyD88, IL-1β, TNF-α compared with PBS control after infection. In BALB/c mice abdominal cavity extracted macrophages, pretreatment with Boxb increased the expressions of TLR4, HMGB1, MyD88, IL-1β, TNF-α, while pretreatment with CLI-095 and Boxb significantly decreased the expressions of TLR4, HMGB1, MyD88, IL-1β, TNF-α. CONCLUSION In A. fumigatus keratitis, Boxb play a pro-inflammatory role in corneal anti-fungi immune response through the HMGB1-TLR4-MyD88 signal pathway.