The role of transforming growth factor-?2 in cigarette smoke-induced lung inflammation and injury

被引：4
作者：
Ko, Hsin-Kuo [1 ,2 ]
Hsiao, Yi-Han [1 ,2 ,3 ,4 ]
Jeng, Mei-Jy [5 ,6 ]
Yang, De-Ming [7 ,8 ]
Chen, Pei-Ku [9 ,10 ]
Su, Kang-Cheng [1 ,2 ]
Chou, Kun-Ta [1 ,2 ]
Perng, Diahn-Warng [1 ,2 ,11 ]
机构：
[1] Taipei Vet Gen Hosp, Dept Chest Med, Taipei 11217, Taiwan
[2] Natl Yang Ming Chiao Tung Univ, Coll Med, Taipei 11221, Taiwan
[3] Natl Yang Ming Chiao Tung Univ, Coll Med, Dept Physiol, Taipei 11221, Taiwan
[4] Natl Yang Ming Chiao Tung Univ, Inst Physiol, Coll Med, Taipei 11221, Taiwan
[5] Taipei Vet Gen Hosp, Dept Pediat, Taipei 11217, Taiwan
[6] Natl Yang Ming Chiao Tung Univ, Inst Emergency & Crit Care Med, Coll Med, Taipei 11221, Taiwan
[7] Taipei Vet Gen Hosp, Dept Med Res, Div Basic Res, Taipei 11217, Taiwan
[8] Natl Yang Ming Chiao Tung Univ, Inst Biophoton, Coll Biomed Sci & Engn, Taipei 11221, Taiwan
[9] Taipei Municipal Gan Dau Hosp, Managed Taipei Vet Gen Hosp, Dept Med Affairs, Taipei 11260, Taiwan
[10] Natl Yang Ming Chiao Tung Univ, Inst Microbiol & Immunol, Sch Life Sci, Taipei 11221, Taiwan
[11] Taipei Vet Gen Hosp, Dept Chest Med, 201, Sec 2, Shih Pai Rd, Taipei 112, Taiwan
来源：
LIFE SCIENCES | 2023年 / 320卷
关键词：
Cigarette smoke; Smad; 3; Signaling pathway; Lung epithelial cell; Lung inflammation; TGF-?2; ACTIVATED PROTEIN-KINASE; P38 MAP KINASE; FACTOR-BETA; TGF-BETA; EPITHELIAL-CELLS; ALK5; INHIBITOR; FIBROSIS; EXPRESSION; ASTHMA; INDUCTION;
D O I：
10.1016/j.lfs.2023.121539
中图分类号：
R-3 [医学研究方法]; R3 [基础医学];
学科分类号：
1001 ;
摘要：
Aims: Transforming growth factor-beta 2 (TGF-beta 2) plays an important role in pleiotropic functions and has been reported to be involved in the pathogenesis of chronic obstructive lung disease. The role of TGF-beta 2 in regulating cigarette smoke (CS)-induced lung inflammation and injury has not been investigated, and its underlying mechanism remains unclear.Main methods: Primary bronchial epithelial cells (PBECs) were treated with cigarette smoke extract (CSE), and the signaling pathway of TGF-beta 2 regulating lung inflammation was investigated. Mice were exposed to CS and treated with TGF-beta 2 i.p. or bovine whey protein extract containing TGF-beta 2 p.o., and the role of TGF-beta 2 in alleviating lung inflammation/injury was studied.Key findings: In vitro, we demonstrated that TGF-beta 2 attenuated CSE-induced IL-8 production from PBECs through the TGF-beta receptor I (TGF-beta RI), Smad3, and mitogen-activated protein kinase signaling pathways. Selective TGF beta RI inhibitor (LY364947) and antagonist of Smad3 (SIS3) abolished the effect of TGF-beta 2 on alleviating CSEinduced IL-8 production. In vivo, CS exposure for 4 weeks in mice increased the levels of total protein, inflammatory cell counts, and monocyte chemoattractant protein-1 in bronchoalveolar fluid and induced lung inflammation/injury, as revealed by immunohistochemistry. Administration of TGF-beta 2 through intraperitoneal injection or oral feeding with bovine whey protein extract containing TGF-beta 2 significantly reduced CS-induced lung inflammation and injury.Significance: We concluded that TGF-beta 2 reduced CSE-induced IL-8 production through the Smad3 signaling pathway in PBECs and alleviated lung inflammation/injury in CS-exposed mice. The anti-inflammatory effect of TGF-beta 2 on CS-induced lung inflammation in humans deserves further clinical study.
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页数：10
相关论文
共 56 条
[1]   Orally administered TGF-β is biologically active in the intestinal mucosa and enhances oral tolerance [J].
Ando, Takashi ;
Hatsushika, Kyosuke ;
Wako, Masanori ;
Ohba, Tetsuro ;
Koyama, Kensuke ;
Ohnuma, Yuko ;
Katoh, Ryohei ;
Ogawa, Hideoki ;
Okumura, Ko ;
Luo, Jian ;
Wyss-Coray, Tony ;
Nakao, Atsuhito .
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 2007, 120 (04) :916-923
[2]   Cigarette Smoke Induces the Risk of Metabolic Bone Diseases: Transforming Growth Factor Beta Signaling Impairment via Dysfunctional Primary Cilia Affects Migration, Proliferation, and Differentiation of Human Mesenchymal Stem Cells [J].
Aspera-Werz, Romina H. ;
Chen, Tao ;
Ehnert, Sabrina ;
Zhu, Sheng ;
Froehlich, Theresa ;
Nussler, Andreas K. .
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2019, 20 (12)
[3]   Increased TGF-β2 in severe asthma with eosinophilia [J].
Balzar, S ;
Chu, HW ;
Silkoff, P ;
Cundall, M ;
Trudeau, JB ;
Strand, M ;
Wenzel, S .
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 2005, 115 (01) :110-117
[4]   Oxidative stress-based therapeutics in COPD [J].
Barnes, Peter J. .
REDOX BIOLOGY, 2020, 33
[5]   Transforming growth factor beta (TGF-β) and inflammation in cancer [J].
Bierie, Brian ;
Moses, Harold L. .
CYTOKINE & GROWTH FACTOR REVIEWS, 2010, 21 (01) :49-59
[6]   MAP3K19 Is Overexpressed in COPD and Is a Central Mediator of Cigarette Smoke-Induced Pulmonary Inflammation and Lower Airway Destruction [J].
Boehme, Stefen A. ;
Franz-Bacon, Karin ;
Ludka, John ;
DiTirro, Danielle N. ;
Ly, Tai Wei ;
Bacon, Kevin B. .
PLOS ONE, 2016, 11 (12)
[7]   Progressive transforming growth factor β1-induced lung fibrosis is blocked by an orally active ALK5 kinase inhibitor [J].
Bonniaud, P ;
Margetts, PJ ;
Kolb, M ;
Schroeder, JA ;
Kapoun, AM ;
Damm, D ;
Murphy, A ;
Chakravarty, S ;
Dugar, S ;
Higgins, L ;
Protter, AA ;
Gauldie, J .
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 2005, 171 (08) :889-898
[8]   TGF-β Isoform Specific Regulation of Airway Inflammation and Remodelling in a Murine Model of Asthma [J].
Bottoms, Stephen E. ;
Howell, Jane E. ;
Reinhardt, Alistair K. ;
Evans, Iona C. ;
McAnulty, Robin J. .
PLOS ONE, 2010, 5 (03)
[9]   Genetic analysis of the mammalian transforming growth factor-β superfamily [J].
Chang, H ;
Brown, CW ;
Matzuk, MM .
ENDOCRINE REVIEWS, 2002, 23 (06) :787-823
[10]   A bovine whey protein extract can induce the generation of regulatory T cells and shows potential to alleviate asthma symptoms in a murine asthma model [J].
Chen, Jiunn-Horng ;
Huang, Po-Han ;
Lee, Chen-Chen ;
Chen, Pin-Yu ;
Chen, Hui-Chen .
BRITISH JOURNAL OF NUTRITION, 2013, 109 (10) :1813-1820
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