Role of the TSLP-DC-OX40L pathway in asthma pathogenesis and airway inflammation in mice (Retracted article. See MAR, 2023)
Role of the TSLP-DC-OX40L pathway in asthma pathogenesis and airway inflammation in mice (Retracted article. See MAR, 2023)
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DOI：
10.1139/bcb-2017-0126
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发表时间：
2018-06-01
影响因子：
2.9
通讯作者：
Shi, Rui-Ming
中科院分区：
文献类型：
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作者：
Feng, Shuang;Zhang, Li;Shi, Rui-Ming
本研究旨在探讨TLP-DC-OX 40 L通路在小鼠哮喘发病机制及气道炎症中的作用。为此，将65只雄性BALF/c小鼠分配在对照组、哮喘组、免疫球蛋白G（IgG）+哮喘组中（IgG，500 μ g/500 μ L，每次腹腔注射50 μ L），LY 294002（OX 40 L抑制剂）+哮喘抗TSLP+哮喘（TSLP抗体500 μ g/500 μ L，每次50 μ L）组。采用ELISA法检测血清免疫球蛋白E（IgE）、卵清蛋白（OVA）-sIgE、白细胞介素-4（IL-4）、IL-5、IL-13、干扰素-γ（IFN-γ）水平;流式细胞术检测Treg细胞、树突状细胞（DC）和淋巴细胞生成。采用RT-qPCR和Western印迹法测定TSLP、OX 40 L、T-bet、加塔-3、NF-κ B、p38和ERK的水平。用LY 294002和抗TSLP治疗导致支气管肺泡灌洗液中总细胞、嗜酸性粒细胞、中性粒细胞和淋巴细胞的数量增加; IgE、OVA-sIgE、IL-4、IL-5和IL-13的总血清水平增加; DC细胞水平增加;淋巴细胞生成增加;以及TSLP、OX 40 L、加塔-3、NF-κ B、p38和ERK的水平，而IFN-（γ）和CD 4（+）CD 25（+）Treg细胞、CD 4（+）Foxp 3（+）Treg细胞和T-bet的水平降低。TSLP-DC-OX 40 L通路可能通过调节CD 4（+）CD 25（+）Treg细胞和炎性细胞因子的水平参与哮喘发病和气道炎症。
This study aimed to explore the effect of the TSLP-DC-OX40L pathway in asthma pathogenesis and airway inflammation in mice. For this, 65 male BALF/c mice were distributed among the control, asthma, immunoglobulin G (IgG) + asthma (IgG, 500 mu g/500 mu L, intratracheal injection of 50 mu L each time), LY294002 (OX40L inhibitor) + asthma (intratracheal injection of 2 mg/kg LY294002), and anti-TSLP + asthma (intratracheal injection of 500 mu g/500 mu L TSLP antibody, 50 mu L each time) groups. ELISA was applied to measure the serum levels of immunoglobulin E (IgE), ovalbumin (OVA)-sIgE, interleukin-4 (IL-4), IL-5, IL-13, and interferon-gamma (IFN-gamma); flow cytometry was employed to detect Treg cells and dendritic cell (DC) and lymphopoiesis. RT-qPCR and Western blot assays were used to measure the levels of TSLP, OX40L, T-bet, GATA-3, NF-kappa B, p38, and ERK. Treatment with LY294002 and anti-TSLP resulted in increases in the numbers of total cells, eosinophils, neutrophils, and lymphocytes in the bronchoalveolar lavage fluid; total serum levels of IgE, OVA-sIgE, IL-4, IL-5, and IL-13; levels of DC cells; lymphopoiesis; and levels of TSLP, OX40L, GATA-3, NF-kappa B,p38, and ERK, whereas there were decreases in the levels of IFN-(gamma) and CD4(+)CD25(+) Treg cells; CD4(+)Foxp3(+) Treg cells; and T-bet. The TSLP-DC-OX40L pathway may contribute to asthma pathogenesis and airway inflammation by modulating the levels of CD4(+)CD25(+) Treg cells and inflammatory cytokines.