title: [HMGB1/TLR4/NF-κB signaling pathway and role of vitamin D in asthmatic mice].
abstract: 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)2D3intervention 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)2D3has a regulatory effect on this pathway and may prevent the progression of asthma. Therefore, 1,25-(OH)2D3is expected to become a new choice for the treatment of asthma.
authors.affiliation: Department of Pediatrics, Third Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China. junying.qiao@163.com.
authors.forename: Jun-Ying
authors.initials: JY
authors.lastname: Qiao
authors.forename: Li
authors.initials: L
authors.lastname: Song
authors.forename: Yan-Li
authors.initials: YL
authors.lastname: Zhang
authors.forename: Bin
authors.initials: B
authors.lastname: Luan
mesh_terms: D000818:Animals; D001249:Asthma / Q000188:drug therapy / Q000209:etiology* / Q000473:pathology; D002117:Calcitriol / Q000627:therapeutic use*; D005260:Female; D024243:HMGB1 Protein / Q000032:analysis / Q000502:physiology*; D008168:Lung / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000032:analysis / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D051197:Toll-Like Receptor 4 / Q000032:analysis / Q000502:physiology*
chemical_list: D024243:HMGB1 Protein; C582808:HMGB1 protein, mouse; D016328:NF-kappa B; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D002117:Calcitriol