The effects of Ang-1, IL-8 and TGF-β1 on the pathogenesis of COPD

Gao,Jixu; Zhan,Bingyan

doi:10.3892/mmr.2012.1059

The effects of Ang-1, IL-8 and TGF-β1 on the pathogenesis of COPD

Authors:
- Jixu Gao
- Bingyan Zhan
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Affiliations: Department of Respiratory Medicine, Jiaozhou Central Hospital, Qingdao, Shandong, P.R. China
Published online on: September 3, 2012 https://doi.org/10.3892/mmr.2012.1059
Pages: 1155-1159

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Abstract

Chronic obstructive pulmonary disease (COPD) is a prevalent smoking-related disease for which no disease‑altering therapies currently exist. Airway remodeling is one of the most important mechanisms in the pathogenesis of COPD and is triggered by chronic inflammation mediated by angiopoietin-1 (Ang-1), interleukin-8 (IL-8) and transforming growth factor-β1 (TGF-β1). The aim of this study was to investigate the effects of Ang-1, IL-8 and TGF-β1 on the pathogenesis of COPD. Forty-two COPD patients and 10 healthy adults (group A) were included in this study. We divided the 42 patients into 4 groups (groups B-E) according to the severity of the disease. We investigated the levels of Ang-1, IL-8 and TGF-β1 and the levels of pulmonary function (PF) in the stable and acute phases of COPD by enzyme-linked immunosorbent assay. We found statistically significant differences in the expression levels of Ang-1, IL-8 and TGF-β1 between the stable and acute phases in groups B-E. We found statistically significant differences in the expression levels of Ang-1 among all groups in the stable phase. In addition, there were statistically significant differences in the expression levels of TGF-β1 among all groups. There were statistically significant differences in the expression levels of IL-8 between group A and the other groups in the stable phase. Furthermore, in groups C-E we found higher correlations between Ang-1 and the forced expiratory volume in one second of forced vital capacity (FVC) [FEV1(%)] and FEV1/FVC(%) than between TGF-β1 and FEV1(%) and FEV1/FVC(%). We conclude that the blood vessel factor is more closely related to the pathogenesis of COPD.

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1	Jiangtao L: Expert consensus in difficult therapy-resistant asthma. Chin J Tuberc Respir Dis. 33:572–577. 2010.(In Chinese).
2	Saetta M, Turato G, Maestrelli P, Mapp CE and Fabbri LM: Cellular and structural bases of chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 163:1304–1309. 2001. View Article : Google Scholar : PubMed/NCBI
3	Maestrelli P, Saetta M, Mapp CE and Fabbri LM: Remodeling in response to infection and injury. Airway inflammation and hypersecretion of mucus in smoking subjects with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 164:S76–S80. 2001. View Article : Google Scholar : PubMed/NCBI
4	Lu Q: Transforming growth factor-beta1 protects against pulmonary artery endothelial cell apoptosis via ALK5. Am J Physiol Lung Cell Mol Physiol. 295:L123–L133. 2008. View Article : Google Scholar : PubMed/NCBI
5	Kugathasan L, Ray JB, Deng Y, Rezaei E, Dumont DJ and Stewart DJ: The angiopietin-1-Tie2 pathway prevents rather than promotes pulmonary arterial hypertension in transgenic mice. J Exp Med. 206:2221–2234. 2009. View Article : Google Scholar : PubMed/NCBI
6	Nakamura H, Yoshimura K, McElvaney NG and Crystal RG: Neutrophil elastase in respiratory epithelial lining fluid of individuals with cystic fibrosis induces interleukin-8 gene expression in a human bronchial epithelial cell line. J Clin Invest. 89:1478–1484. 1992. View Article : Google Scholar
7	Chung KF: Airway smooth muscle cells: contributing to and regulating airway mucosal inflammation? Eur Respir J. 15:961–968. 2000. View Article : Google Scholar : PubMed/NCBI
8	Baarsma HA, Spanjer AI, Haitsma G, Engelbertink LH, Meurs H, Jonker MR, Timens W, Postma DS, Kerstjens HA and Gosens R: Activation of WNT/β-catenin signaling in pulmonary fibroblasts by TGF-β₁ is increased in chronic obstructive pulmonary disease. PLoS One. 6:e254502011.
9	Vignola AM, Chanez P, Chiappara G, Merendino A, Zinnanti E, Bousquet J, Bellia V and Bonsignore G: Release of transforming growth factor-β (TGF-β) and fibronectin by alveolar macrophages in airway diseases. Clin Exp Immunol. 106:114–119. 1996.
10	Yancopoulos GD, Davis S, Gale NW, Rudge JS, Wiegand SJ and Holash J: Vascular-specific growth factors and blood vessel formation. Nature. 407:242–248. 2000. View Article : Google Scholar : PubMed/NCBI
11	Thurston G, Rudge JS, Ioffe E, Zhou H, Ross L, Croll SD, Glazer N, Holash J, McDonald DM and Yancopoulos GD: Angiopoietin-1 protects the adult vasculature against plasma leakage. Nat Med. 6:460–463. 2000. View Article : Google Scholar : PubMed/NCBI
12	Saito M, Hamasaki M and Shibuya M: Induction of tube formation by angiopoietin-1 in endothelial cell/fibroblast co-culture is dependent on endogenous VEGF. Cancer Sci. 94:782–790. 2003. View Article : Google Scholar : PubMed/NCBI
13	DunnGalvin A: Sex and gender differences in COPD: challenging the stereotypes. Prim Care Respir J. 20:378–379. 2011. View Article : Google Scholar : PubMed/NCBI
14	Jorens PG, Van Damme J, De Backer W, Bossaert L, De Jongh RF, Herman AG and Rampart M: Interleukin-8 (IL-8) in the bronchoalveolar lavage fluid from patients with the adult respiratory distress syndrome (ARDS) and patients at risk for ARDS. Cytokine. 4:592–597. 1992. View Article : Google Scholar : PubMed/NCBI
15	Keatings VM, Collins PD, Scott DM and Barnes PJ: Differences in interleukin-8 and tumor necrosis factor-α in induced sputum from patients with chronic obstructive pulmonary disease or asthma. Am J Respir Crit Care Med. 153:530–534. 1996.
16	Yamamoto C, Yoneda T, Yoshikawa M, Fu A, Tokuyama T, Tsukaguchi K and Narita N: Airway inflammation in COPD assessed by sputum levels of interleukin-8. Chest. 112:505–510. 1997. View Article : Google Scholar : PubMed/NCBI
17	Bhowmik A, Seemungal TA, Sapsford RJ and Wedzicha JA: Relation of sputum inflammatory markers to symptoms and lung function changes in COPD exacerbations. Thorax. 55:114–120. 2000. View Article : Google Scholar : PubMed/NCBI
18	Stockley RA: Inflammation and acute exacerbations of chronic bronchitis. Chest. 120:1422–1423. 2001. View Article : Google Scholar : PubMed/NCBI
19	Trevino JG, Gray MJ, Nawrocki ST, Summy JM, Lesslie DP, Evans DB, Sawyer TK, Shakespeare WC, Watowich SS, Chiao PJ, et al: Src activation of Stat3 is an independent requirement from NF-κB activation for constitutive IL-8 expression in human pancreatic adenocarcinoma cells. Angiogenesis. 9:101–110. 2006.PubMed/NCBI
20	Zhou F, Onizawa S, Nagai A and Aoshiba K: Epithelial cell senescence impairs repair process and exacerbates inflammation after airway injury. Respir Res. 12:78–83. 2011. View Article : Google Scholar : PubMed/NCBI
21	Rennard SI and Wachenfeldt K: Rationale and emerging approaches for targeting lung repair and regeneration in the treatment of chronic obstructive pulmonary disease. Proc Am Thorac Soc. 8:368–375. 2011. View Article : Google Scholar : PubMed/NCBI
22	Parameswaran K, Willems-Widyastuti A, Alagappan VK, Radford K, Kranenburg AR and Sharma HS: Role of extracellular matrix and its regulators in human airway smooth muscle biology. Cell Biochem Biophys. 44:139–146. 2006. View Article : Google Scholar : PubMed/NCBI
23	Korfhagen TR, Swantz RJ, Wert SE, McCarty JM, Kerlakian CB, Glasser SW and Whitsett JA: Respiratory epithelial cell expression of human transforming growth factor-alpha induces lung fibrosis in transgenic mice. J Clin Invest. 93:1691–1699. 1994. View Article : Google Scholar : PubMed/NCBI
24	Rock JR, Randell SH and Hogan BL: Airway basal stem cells: a perspective on their roles in epithelial homeostasis and remodeling. Dis Model Mech. 3:545–556. 2010. View Article : Google Scholar : PubMed/NCBI
25	Zhang J, Wu L, Feng MX, Sexton P, Bai CX, Qu JM, Merrilees M and Black PN: Pulmonary fibroblasts from COPD patients show an impaired response of elastin synthesis to TGF-β1. Respir Physiol Neurobiol. 177:236–240. 2011.PubMed/NCBI
26	Teisanu RM, Chen H, Matsumoto K, McQualter JL, Potts E, Foster WM, Bertoncello I and Stripp BR: Functional analysis of two distinct bronchiolar progenitors during lung injury and repair. Am J Respir Cell Mol Biol. 44:794–803. 2011. View Article : Google Scholar : PubMed/NCBI
27	Ichimaru Y, Krimmer DI, Burgess JK, Black JL and Oliver BG: TGF-β enhances deposition of perlecan from COPD airway smooth muscle. Am J Physiol Lung Cell Mol Physiol. 302:L325–L333. 2012.
28	Song Y, Cui D and Mao P: The potential role of growth factor in the airway wall remodeling of a chronic obstructive pulmonary disease rat model and the effects of drugs on them. Zhonghua Nei Ke Za Zhi. 39:751–754. 2000.(In Chinese).
29	Bakhshayesh M, Zaker F, Hashemi M, et al: TGF-β1-mediated apoptosis associated with SMAD-dependent mitochondrial Bcl-2 expression. Clin Lymphoma Myeloma Leuk. 12:138–143. 2012.
30	Nishishita T and Lin PC: Angiopoietin-1, PDGF-B, and TGF-beta gene regulation in endothelial cell and smooth muscle cell interaction. J Cell Biochem. 91:584–593. 2004. View Article : Google Scholar : PubMed/NCBI
31	Fadok VA, Bratton DL, Konowai A, Freed PW, Westcott JY and Henson PM: Macrophages that have ingested apoptotic cells in vitro inhibit proinflammatory cytokine production through autocrine/paracrine mechanisms involving TGFβ, PGE2 and PAF. J Clin Invest. 101:890–898. 1998.PubMed/NCBI
32	Wente MN, Keane MP, Burdick MD, Friess H, Büchler MW, Ceyhan GO, Reber HA, Strieter RM and Hines OJ: Blockade of the chemokine receptor CXCR2 inhibits pancreatic cancer cell-induced angiogenesis. Cancer Lett. 241:221–227. 2006. View Article : Google Scholar : PubMed/NCBI
33	Cho YJ, Ma JE, Yun EY, Kim YE, Kim HC, Lee JD, Hwang YS and Jeong YY: Serum angiopoietin-2 levels are elevated during acute exacerbations of COPD. Respirology. 16:284–290. 2011. View Article : Google Scholar : PubMed/NCBI
34	Yamato H, Sun JP, Churg A and Wright JL: Cigarette smoke-induced emphysema in guinea pigs is associated with diffusely decreased capillary density and capillary narrowing. Lab Invest. 75:211–219. 1996.PubMed/NCBI