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HMGB1/TLR4/NF-κB signaling pathway and role of vitamin D in asthmatic mice
QIAO Jun-Ying, SONG Li, ZHANG Yan-Li, LUAN Bin
Chinese Journal of Contemporary Pediatrics ›› 2017, Vol. 19 ›› Issue (1) : 95-103.
PDF(3762 KB)
PDF(3762 KB)
HMGB1/TLR4/NF-κB signaling pathway and role of vitamin D in asthmatic mice
Objective To investigate the changes in the mRNA and protein expression of high-mobility group box 1 (HMGB1), Toll-like receptor 4 (TLR4), and nuclear factor-kappa B (NF-κB) in lung tissues of asthmatic mice and the interventional effect of vitamin D. Methods A total of 48 BALB/c mice were randomly divided into control group, asthma group, and 1,25-(OH)2D3 intervention group, with 16 mice in each group. An animal model of asthma was established, and lung tissue samples were taken in each group at weeks 1 and 2 of ovalbumin challenging. Conventional hematoxylin-eosin staining was used to measure airway wall thickness. Immunohistochemical staining was used to observe the expression of HMGB1, TLR4, and NF-κB in lung tissues. Quantitative real-time PCR and Western blot were used to investigate the changes in the mRNA and protein expression of HMGB1, TLR4, and NF-κB. Results At weeks 1 and 2 of ovalbumin challenging, compared with the control group, the asthma group had a significant increase in airway wall thickness and the intervention group had a significant reduction compared with the asthma group (P < 0.05). The asthma group had significantly higher mRNA expression of HMGB1, TLR4, and NF-κB in lung tissues than the control group, and the intervention group had significantly lower mRNA expression of TLR4 and NF-κB than the asthma group (P < 0.05). At week 1 of ovalbumin challenging, there was no significant difference in the mRNA expression of HMGB1 between the intervention group and the asthma group (P > 0.05). At week 2, the intervention group had a significant reduction in the mRNA expression of HMGB1 compared with the asthma group (P < 0.05). At weeks 1 and 2 of ovalbumin challenging, the asthma group had significantly higher protein expression of HMGB1, TLR4, and NF-κB in lung tissues than the control group, and the intervention group had significantly lower expression than the asthma group (P < 0.05). Airway wall thickness was positively correlated with the mRNA expression of HMGB1, TLR4, and NF-κB in lung tissues (r=0.804, 0.895, and 0.834; P < 0.05). Conclusions The HMGB1/TLR4/NF-κB signaling pathway plays an important role in the pathogenesis of asthma, and an appropriate amount of 1,25-(OH)2D3 has a regulatory effect on this pathway and may prevent the progression of asthma. Therefore, 1,25-(OH)2D3 is expected to become a new choice for the treatment of asthma.
High-mobility group box 1 / Toll-like receptor 4 / Nuclear factor-kappa B / Asthma / Vitamin D / Mice
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