Journal of Shandong University (Health Sciences) ›› 2020, Vol. 58 ›› Issue (4): 78-83.doi: 10.6040/j.issn.1671-7554.0.2019.1345

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Airway smooth muscle cells regulate IL-33 expression through TGF-β1/Smad3 signaling pathway to participate in asthma

CAI Qiujing, ZHANG Qian, HE Xuejia, SUN Wenli, GUO Aili, ZHANG Nan, ZHU Weiwei   

  1. Department of Pediatrics, Jinan Central Hospital Affiliated to Shandong University, Jinan 250013, Shandong, China
  • Published:2022-09-27

Abstract: Objective To investigate the signaling mechanism of interleukin(IL)-33 expression and secretion in mouse airway smooth muscle cells. Methods To observe the effect of TGF-β1 with different concentrations(0 ng/mL, 1 ng/mL, 10 ng/mL, 100 ng/mL)on the secretion and expression of IL-33 in mouse airway smooth muscle cells. ELISA was used to detect the concentration of IL-3 in cell culture supernatant of each group. Western blotting was used to detect the expression of IL-33 protein. The inhibitory effect of TGF-β1/Smad3 signaling pathway blocker(SIS3)was observed and the cells were divided into blank group, pretreated TGF-β1 group, unpretreated SIS3 group and pretreated SIS3 group. ELISA was used to detect the concentration of IL-33 in the cell culture supernatant, and Western blotting was used to detect the expressions of Smad3, pSmad3 and IL-33 protein in each group. Results ELISA result showed that the cellular IL-33 concentration in the blank group, 1ng/mL TGF-β1 group, 10 ng/mL TGF-β1 group and 100 ng/mL TGF-β1 group were statistically different (F=106.4, P<0.05). Compared with the blank group, the IL-33 concentration of 10 ng/mL TGF-β1 group and 100 ng/mL TGF-β1 group were increased(P<0.008 3). The IL-33 concentration of 10 ng/mL TGF-β1 group was higher than that of 1ng/mL TGF-β1 group and 100 ng/mL TGF-β1 group(P<0.008 3). Western blotting result showed that the IL-33 protein expression in blank group, 1 ng/mL TGF-β1 group, 10 ng/mL TGF-β1 group and 100 ng/mL TGF-β1 group was statistically different (F=1 613.0, P<0.05). There exists statiscical difference between each two groups with the most significant increase of IL-33 expression in 10 ng/mL TGF-β1 group(P<0.008 3). Westerm blotting result showed that the IL-33 concentration in blank group, pretreatment TGF-β1 group, unpretreatment SIS3 group and pretreatment SIS3 group was statistically different (F=166.7, P<0.05). Compared with the blank group, the IL-33 concentration of pretreatment TGF-β1 group, unpretreatment SIS3 group and pretreatment SIS3 group were increased(P<0.05). There were statistical difference of Smad3, pSmad3, IL-33 protein expressions among the blank group, pretreatment TGF-β1 group, unpretreatment SIS3 group and pretreatment SIS3 group[(F=4 752.0,P<0.05),(F=4 330.0,P<0.05),(F=2 791.0,P<0.05)]. Compared with the blank group, the Smad3, pSmad3 and IL-33 protein expressions were increased in pretreatment TGF-β1 group and pretreatment SIS3 group while those decreased in unpretreatment SIS3 group(P<0.05). Conclusion TGF- β1 with a certain concentration can stimulate the expression and secretion of IL-33 in mouse airway smooth muscle cells, and TGF-β1/Smad3 signaling pathway can regulate this process involved in the asthma mechanism.

Key words: Transforming growth factor-β1/Smad3 signal pathway, Interluekin-33, Mouse airway smooth muscle cell, Asthma

CLC Number: 

  • R574
[1] Castro-Rodriguez JA, Saglani S, Rodriguez-Martinez CE, et al. The relationship between inflammation and remodeling in childhood asthma: a systematic review[J]. Pediatr Pulmonol, 2018, 53(6): 824-835.
[2] James AL, Elliot JG, Jones RL, et al. Airway smooth muscle hypertrophy and hyperplasia in asthma[J]. Am J Respir Crit Care Med, 2012, 185(10): 1058-1064.
[3] Salter B, Pray C, Radford K, et al. Regulation of human airway smooth muscle cell migration and relevance to asthma[J]. Respir Res, 2017, 18(1): 156. doi: 10.1186/s12931-017-0640-8.
[4] Royce SG, Cheng V, Samuel CS. The regulation of fibrosis in airway remodeling in asthma[J]. Mol Cell Endocrinol, 2012, 351(2): 167-175.
[5] Yoshida K, Murata M, Yamaguchi T, et al. TGF-β/Smad signaling during hepatic fibro-carcinogenesis(review)[J]. Int J Oncol, 2014, 45(4): 1363-1371.
[6] Drake LY, Kita H. IL-33: biological properties, functions, and roles in airway disease[J]. Immunol Rev, 2017, 278(1): 173-184.
[7] Cayrol C, Girard JP. IL-33: an alarmin cytokine with crucial roles in innate immunity, inflammation and allergy[J]. Curr Opin Immunol, 2014, 31: 31-37. doi: 10.1016/j.coi.2014.09.004.
[8] Préfontaine D, Lajoie-Kadoch S, Foley S, et al. Increased expression of IL-33 in severe asthma: evidence of expression by airway smooth muscle cells[J]. J Immunol, 2009, 183(8): 5094-5103.
[9] 舒萍.免疫调节剂对小儿哮喘的治疗应用综述[J]. 中国药物经济学, 2016,11(10):19-21.
[10] Estrada RD, Ownby DR. Rural asthma: current understanding of prevalence, patterns, and interventions for children and adolescents[J]. Curr Allergy Asthma Rep, 2017, 17(6): 37. doi: 10.1007/s11882-017-0704-3.
[11] James Alan. Airway remodeling in asthma: is it fixed or variable?[J]. Am J Respir Crit Care Med, 2017, 195(8): 968-970.
[12] 阳志华, 莫碧文. 气道平滑肌细胞在哮喘中的作用研究进展[J]. 世界最新医学信息文摘, 2018, 18(6):70-80,83. YANG Zhihua, MO Biwen. Role of airway smooth muscle cells in asthma mechanisms[J]. World Latest Medicine Information(Electronic Versioin), 2018,18(6):70-80,83.
[13] Kwak HJ, Park DW, Seo JY, et al. The Wnt/β-catenin signaling pathway regulates the development of airway remodeling in patients with asthma[J]. Exp Mol Med, 2015, 47: e198. doi: 10.1038/emm.2015.91.
[14] Johansson K, McSorley HJ. Interleukin-33 in the developing lung-Roles in asthma and infection.[J]. Pediatric Allergy Immunol, 2019, 30(5): 503-510.
[15] Cayrol C, Girard JP. Interleukin-33(IL-33): a nuclear cytokine from the IL-1 family[J]. Immunol Rev, 2018, 281(1): 154-168.
[16] Gabryelska A, Kuna P, Antczak A, et al. IL-33 mediated inflammation in chronic respiratory diseases-understanding the role of the member of IL-1 superfamily[J]. Front Immunol, 2019, 10: 692. doi: 10.3389/fimmu.2019.00692.
[17] Gupta RK, Gupta K, Dwivedi PD. Pathophysiology of IL-33 and IL-17 in allergic disorders[J]. Cytokine Growth Factor Rev, 2017, 38: 22-36. doi: 10.1016/j.cytogfr.2017.09.005.
[18] 刘力维, 赵霞. TGF-β1/Smad信号通路与哮喘气道重塑的关系及研究进展[J]. 辽宁中医杂志, 2015,42(9): 1811-1813. LIU Liwei, ZHAO Xia. Relation between TGF-β/Smadand airway remodeling in asthma and its research progress[J]. Liaoning Journal of Traditional Chinese Medicine, 2015,42(9): 1811-1813.
[19] 沈豪, 郭霜, 刘秀芬, 等. TGF-β/Smads信号通路在姜黄素改善糖尿病大鼠心肌纤维化中的作用[J]. 中国药理学通报,2018,34(4): 522-527. SHEN Hao, GUO Shuang, LIU Xiufen, et al. Curcumin ameliorates myocardial fibrosis via TGF-β/Smads signaling pathway in diabetic rats[J]. Chinese Pharmacological Bulletin, 2018,34(4): 522-527.
[20] Chen M, Huang L, Zhang W, et al. MiR-23b controls TGF-β1 induced airway smooth muscle cell proliferation via TGFβR2/p-Smad3 signals[J]. Mol Immunol, 2016, 70: 84-93. doi: 10.1016/j.molimm.2015.12.012.
[21] 田彦, 崔红生, 张鑫. 三步序贯法对激素依赖型哮喘患者TGF-β1/Smad信号通路及肺功能的影响[J]. 中华中医药杂志, 2019,34(9): 4413-4416. TIAN Yan, CUI Hongsheng, ZHANG Xin. Influence of three-stage sequential therapy on TGF-β1/Smad signaling pathway and lung function of steroid-dependent asthma patients[J]. CJTCMP, 2019,34(9): 4413-4416.
[22] 张云珍, 方海燕, 余红, 等. 白藜芦醇抑制TGF-β1/Smad3信号通路对人肺上皮细胞A549 EMT调控的影响及机制[J]. 广东医学,2019,40(15):2130-2134. ZHANG Yunzhen, FANG Haiyan, YU Hong, et al. Study of the effects and the mechanisms of resveratrol on the regulation of human pulmonary epithelial cell A549 by inhibiting TGF-β1/Smad3 signaling pathway[J]. Guangdong Medical Journal, 2019,40(15):2130-2134.
[23] 蔡亮鸣, 叶慧清, 杨丽芬, 等. TGF-β_1上调Smad3磷酸化对气道上皮细胞表达胸腺基质淋巴细胞生成素的促进作用及其机制[J]. 解放军医学杂志,2019,44(4):281-286. CAI Liangming, YE Huiqing, YANG Lifen, et al. Auxo action and mechanism of TGF-β1 up-regulating Smad3 phosphorylation on the expression of thymic stromal lymphopoietin in human bronchial epithelia[J]. Medical Journal of Chinese Peoples Liberation Army, 2019,44(4):281-286.
[24] Da C, Liu Y, Zhan Y, et al. Nobiletin inhibits epithelial-mesenchymal transition of human non-small cell lung cancer cells by antagonizing the TGF-β1/Smad3 signaling pathway[J]. Oncol Rep, 2016, 35(5): 2767-2774.
[25] 何金婷, 莽靖, 董玥, 等. C-Jun氨基末端激酶与Activin A/Smads通路在体外脑缺血损伤中的相互作用[J]. 中国实验诊断学, 2019, 23(8): 1408-1412. HE Jinting, MANG Jing, DONG Yue, et al. Interactions between C-Jun B-terminal kinase and Activin A/Smads signal in cerebral ischemic injury in vitro[J]. Chinese Journal of Laboratory Diagnosis, 2019, 23(8): 1408-1412.
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