Boxb mediate BALB/c mice corneal inflammation through a TLR4/MyD88-dependent signaling pathway in Aspergillus fumigatus keratitis

• Main Authors: Min Liu, Cui Li, Gui-Qiu Zhao, Jing Lin, Cheng-Ye Che, Qiang Xu, Qian Wang, Rui Xu, Ya-Wen Niu
• Format: Article
• Language: English
• Published: Press of International Journal of Ophthalmology (IJO PRESS) 2018-04-01
• Series: International Journal of Ophthalmology
• Subjects: 552; high-mobility group box 1; Aspergillus fumigatus keratitis; Toll-like receptor 4
• Online Access: http://www.ijo.cn/en_publish/2018/4/20180402.pdf
• ISSN: 2222-3959; 2227-4898

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.