Experimental study on the effects of tumor necrosis factor-α monoclonal antibody on autophagy level in allergic rhinitis mice
10.3760/cma.j.issn.1673-0860.2019.07.007
- VernacularTitle: 肿瘤坏死因子α单克隆抗体对变应性鼻炎小鼠自噬影响的实验研究
- Author:
Shuang ZHANG
1
;
Zhiyong YAN
1
;
Di WANG
1
;
Sainan LI
1
;
Zhi XU
1
;
Qiaofei TANG
1
Author Information
1. Department of Otorhinolaryngology, the Second Affiliated Hospital of Shenyang Medical College, Shenyang 110000, China
- Publication Type:Journal Article
- Keywords:
Rhinitis, allergic;
Tumor necrosis factor-alpha;
Antibodies, monoclonal;
Autophagy
- From:
Chinese Journal of Otorhinolaryngology Head and Neck Surgery
2019;54(7):517-523
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To observe the effect of tumor necrosis factor-α (TNF-α) monoclonal antibody on autophagy in allergic rhinitis (AR) mice.
Methods:Thirty six weeks old BALB/c mice were randomly divided by random number table method into five groups: control group, model group (AR group), TNF-α antibody intervention group (AR+TNF-α group), autophagy inhibitor (3-methylindole, 3-NA) intervention group (AR+3-MA group), TNF-α antibody combined with autophagy inducer rapamycin (RAP) intervention group (AR+TNF-α+RAP group), with 6 mice in each group. AR model was established by conventional method, the corresponding reagent was administered before nasal cavity stimulation sensitization and during the whole experiment. Behavioral scores of mice were obtained, blood was collected from the eye socket, and mice in each group were sacrificed to collect nasal mucosa tissue samples. Pathological changes of nasal mucosa were observed by hematoxylin-eosin staining. Expression levels of inflammatory factor and IgE in serum were detected by enzyme-linked immunosorbent assay (ELISA). Expressions of autophagy related indicators microtubule-associated protein-1 light chain-3B (LC3B), Beclin-1, sequestosome1 (p62), autophagy-related 5 (ATG5), autophagy-related 7 (ATG7) were measured by Real-time PCR and Western blot. The aggregation of LC3B protein was observed by immunofluorescence. SPSS 19.0 software was used for statistical analysis.
Results:Compared with the AR model group, symptoms of AR in AR+TNF-α group and AR+3-MA group were mild; the pathological changes of nasal mucosa were weak; the expression of IgE, TNF-α, interleukin 4 (IL-4), interferon-γ (IFN-γ) in serum significantly reduced (IgE: 666.19±78.35 (±s) vs. 692.38±64.29 vs. 1 059.05±146.44, TNF-α: 112.06±12.95 vs. 113.17±15.43 vs. 161.22±17.96, IL-4: 54.05±7.14 vs. 58.26±5.67 vs. 79.95±6.33, IFN-γ: 28.58±4.51 vs. 30.67±2.60 vs. 39.83±3.31, all P<0.05), and the expression of LC3B Ⅱ/Ⅰ, Beclin-1, ATG5, ATG7 in nasal mucosa significantly decreased, the expression of p62 significantly elevated. After intervention with autophagy inducer RAP, the therapeutic effect of TNF-α monoclonal antibodies on AR was antagonized.
Conclusion:TNF-α monoclonal antibody significantly improves nasal symptoms in AR mice by inhibiting autophagy levels.
