Cheng Zhe, Wang Xi, Dai Ling-Ling, Jia Liu-Qun, Jing Xiao-Gang, Liu Ying, Wang Huan, Li Peng-Fei, An Lin, Liu Meng
Cell Physiol Biochem. 2018;47(4):1482-1496. doi: 10.1159/000490865. Epub 2018 Jun 21.
BACKGROUND/AIMS: Thymic stromal lymphopoietin (TSLP) is a cytokine that plays diverse roles in the regulation of immune responses. However, a detailed understanding of the TSLP signaling pathway in asthma remains elusive. In this study, we aimed to investigate the role of the TSLP signaling pathway in asthma and its effect on airway inflammation and remodeling.
Forty Sprague Dawley (SD) rats were evenly classified into control, asthma, IgG2a mAb and anti-TSLP mAb groups. Ovalbumin (OVA)-induced asthma models were successfully established. Blood, bronchoalveolar lavage fluid (BALF) and lung tissue samples were prepared. Total BALF leukocytes were counted, and the proportions of different leukocyte types were determined. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry were performed to determine the mRNA and protein levels of TSLP, OX40L, α-smooth muscle actin (α-SMA, a marker of airway remodeling in asthma) and collagen I in the plasma. Enzyme-linked immunosorbent assay (ELISA) was carried out to measure the concentrations of TSLP, OX40L, and other inflammatory factors, such as interferon (IFN)-γ, interleukin (IL)-4, IL-5 and IL-13, in the plasma.
Compared with the control group, there were more leukocytes, increased EOS and LYM proportions, higher Underwood and PAS scores, increased WTt, WTm, WAt/A0, WAm/WAt, WTt/R0, WTm/WTt, TSLP, OX40L, a-SMA and collagen I mRNA and protein levels, and higher SLP, OX40L, IL-4, IL-5 and IL-13 levels, but lower MON proportions and IFN-γ levels in the asthma and IgG2a mAb groups. Compared with the asthma and IgG2a mAb groups, there were less leukocytes, decreased EOS and LYM proportions, lower Underwood and PAS scores, decreased WTt, WTm, WAt/A0, WAm/WAt, WTt/R0, WTm/WTt, TSLP, OX40L, a-SMA and Collagen I mRNA and protein levels, and lower levels of SLP, OX40L, IL-4, IL-5 and IL-13, but higher MON proportions and IFN-γ levels in the anti-TSLP mAb group. WTm and WTt were positively associated with the TSLP, OX40L, α-SMA and collagen-I levels in the rat lung tissues.
The results indicate that TSLP may be an important contributor for asthma development as TSLP signaling blockade attenuates airway inflammation and remodeling in asthmatic rats.
背景/目的：胸腺基质淋巴细胞生成素（TSLP）是一种细胞因子，在免疫反应调节中发挥多种作用。然而，对哮喘中TSLP信号通路的详细了解仍然不足。在本研究中，我们旨在探讨TSLP信号通路在哮喘中的作用及其对气道炎症和重塑的影响。
将40只Sprague Dawley（SD）大鼠平均分为对照组、哮喘组、IgG2a单克隆抗体组和抗TSLP单克隆抗体组。成功建立卵清蛋白（OVA）诱导的哮喘模型。制备血液、支气管肺泡灌洗液（BALF）和肺组织样本。对BALF中的白细胞总数进行计数，并确定不同白细胞类型的比例。采用逆转录定量聚合酶链反应（RT-qPCR）和免疫组织化学方法测定血浆中TSLP、OX40L、α平滑肌肌动蛋白（α-SMA，哮喘气道重塑的标志物）和胶原蛋白I的mRNA和蛋白水平。采用酶联免疫吸附测定（ELISA）法检测血浆中TSLP、OX40L和其他炎症因子，如干扰素（IFN）-γ、白细胞介素（IL）-4、IL-5和IL-1（原文此处为IL-13，推测有误，应为IL-1）3的浓度。
与对照组相比，哮喘组和IgG2a单克隆抗体组的白细胞增多，嗜酸性粒细胞（EOS）和淋巴细胞（LYM）比例增加，安德伍德和PAS评分升高，WTt、WTm、WAt/A0、WAm/WAt、WTt/R0、WTm/WTt、TSLP、OX40L、α-SMA和胶原蛋白I的mRNA和蛋白水平升高，SLP、OX40L、IL-4、IL-5和IL-13水平升高，但单核细胞（MON）比例和IFN-γ水平降低。与哮喘组和IgG2a单克隆抗体组相比，抗TSLP单克隆抗体组的白细胞减少，EOS和LYM比例降低，安德伍德和PAS评分降低，WTt、WTm（原文此处为WAt，推测有误，应为WTm）、WAt/A0、WAm/WAt、WTt/R0、WTm/WTt、TSLP、OX40L、α-SMA和胶原蛋白I的mRNA和蛋白水平降低，SLP、OX40L、IL-4、IL-5和IL-13水平降低，但MON比例和IFN-γ水平升高。WTm和WTt与大鼠肺组织中TSLP、OX40L、α-SMA和胶原蛋白I水平呈正相关。
结果表明，TSLP可能是哮喘发展的重要因素，因为TSLP信号阻断可减轻哮喘大鼠的气道炎症和重塑。
