Epigallocatechin gallate improves airway inflammation through TGF‑β1 signaling pathway in asthmatic mice

Shan,Lishen; Kang,Xinyuan; Liu,Fen; Cai,Xuxu; Han,Xiaohua; Shang,Yunxiao

doi:10.3892/mmr.2018.9183

Epigallocatechin gallate improves airway inflammation through TGF‑β1 signaling pathway in asthmatic mice

Authors:
- Lishen Shan
- Xinyuan Kang
- Fen Liu
- Xuxu Cai
- Xiaohua Han
- Yunxiao Shang
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Affiliations: Department of Pediatric Pulmonology, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China, Department of Orthopedics, Shengjing Hospital of China Medical University, Shenyang North New Area, Shenyang, Liaoning 110122, P.R. China
Published online on: June 18, 2018 https://doi.org/10.3892/mmr.2018.9183
Pages: 2088-2096
Copyright: © Shan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The present study aimed to investigate the effect of epigallocatechin gallate (EGCG) on airway inflammation in mice with bronchial asthma, and the regulatory mechanism of transforming growth factor (TGF)‑β1 signaling pathway, so as to provide theoretical basis for research and development of a novel drug for clinical treatment. Mouse models of bronchial asthma were established and injected with dexamethasone and EGCG via the caudal vein. 7 days later, bronchoalveolar tissue was collected for hematoxylin and eosin staining. Determination of airway resistance (AWR) and lung function in mice was detected. Serum was separated for cytometric bead array to detect the changes in inflammatory factors. Bronchoalveolar lavage fluid was collected for eosinophil and neutrophil counts. Fresh blood was obtained for flow cytometry to determine the percentages of Th17 and Treg cells. Bronchovesicular tissue was utilized for western blot assay and reverse transcription‑quantitative polymerase chain reaction to determine the proteins and transcription factors in the TGF‑β1 pathway. EGCG 20 mg/kg significantly reduced asthmatic symptoms, lung inflammatory cell infiltration, and the inflammatory factor levels of interleukin (IL)‑2, IL‑6 and tumor necrosis factor (TNF)‑α. In addition, it increased the levels of inflammatory factors, including IL‑10, diminished the percentage of Th17 cells, increased the percentage of Treg cells, and decreased the expression of TGF‑β1 and phosphorylated (p)‑Smad2/3 expression. Following the inhibition of the TGF‑β1 receptor, the anti‑inflammatory effect of EGCG disappeared, and the expression of TGF‑β1 and p‑Smad2/3 increased. EGCG attenuated airway inflammation in asthmatic mice, decreased the percentage of Th17 cells and increased the percentage of Treg cells. The anti‑inflammatory effect of EGCG is achieved via the TGF‑β1 signaling pathway.

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1	Yu HY, Li XY, Cai ZF, Li L, Shi XZ, Song HX and Liu XJ: Eosinophil cationic protein mRNA expression in children with bronchial asthma. Genet Mol Res. 14:14279–14285. 2015. View Article : Google Scholar : PubMed/NCBI
2	Sussan TE, Gajghate S, Chatterjee S, Mandke P, McCormick S, Sudini K, Kumar S, Breysse PN, Diette GB, Sidhaye VK and Biswal S: Nrf2 reduces allergic asthma in mice through enhanced airway epithelial cytoprotective function. Am J Physiol Lung Cell Mol Physiol. 309:L27–L36. 2015. View Article : Google Scholar : PubMed/NCBI
3	Erokhina IL, Voronchikhin PA, Okovityi SV and Emel'ianova OI: Reaction of population of pulmonary mast cells in rat bronchial asthma under the effect of beta-adrenoreceptor antagonists. Tsitologiia. 55:472–474. 2013.(In Russian). PubMed/NCBI
4	Ciepiela O, Ostafin M and Demkow U: Neutrophils in asthma-a review. Respir Physiol Neurobiol. 209:13–16. 2015. View Article : Google Scholar : PubMed/NCBI
5	Bang BR, Kwon HS, Kim SH, Yoon SY, Choi JD, Hong GH, Park S, Kim TB, Moon HB and Cho YS: Interleukin-32γ suppresses allergic airway inflammation in mouse models of asthma. Am J Respir Cell Mol Biol. 50:1021–1030. 2014. View Article : Google Scholar : PubMed/NCBI
6	Adamek-Guzik T, Czerniawska-Mysik G and Guzik T: Bronchial asthma-a chronic inflammatory disorder. Przegl Lek. 53:12–19. 1996.(In Polish). PubMed/NCBI
7	Zakharyan R and Boyajyan A: Inflammatory cytokine network in schizophrenia. World J Biol Psychiatry. 15:174–187. 2014. View Article : Google Scholar : PubMed/NCBI
8	Nakagome K and Nagata M: Pathogenesis of airway inflammation in bronchial asthma. Auris Nasus Larynx. 38:555–563. 2011. View Article : Google Scholar : PubMed/NCBI
9	Messler S, Kropp S, Episkopou V, Felici A, Würthner J, Lemke R, Jerabek-Willemsen M, Willecke R, Scheu S, Pfeffer K and Wurthner JU: The TGF-β signaling modulators TRAP1/TGFBRAP1 and VPS39/Vam6/TLP are essential for early embryonic development. Immunobiology. 216:343–350. 2011. View Article : Google Scholar : PubMed/NCBI
10	Travis MA and Sheppard D: TGF-β activation and function in immunity. Annu Rev Immunol. 32:51–82. 2014. View Article : Google Scholar : PubMed/NCBI
11	Liu ML, Wang H, Wang ZR, Zhang YF, Chen YQ, Zhu FH, Zhang YQ, Ma J and Li Z: TGF-β1 regulation of estrogen production in mature rat Leydig cells. PLoS one. 8:e601972013. View Article : Google Scholar : PubMed/NCBI
12	Zhou F, Drabsch Y, Dekker TJ, de Vinuesa AG, Li Y, Hawinkels LJ, Sheppard KA, Goumans MJ, Luwor RB, de Vries CJ, et al: Nuclear receptor NR4A1 promotes breast cancer invasion and metastasis by activating TGF-β signalling. Nat Commun. 5:33882014. View Article : Google Scholar : PubMed/NCBI
13	Syed V: TGF-β signaling in cancer. J Cell Biochem. 117:1279–1287. 2016. View Article : Google Scholar : PubMed/NCBI
14	Al-Alawi M, Hassan T and Chotirmall SH: Transforming growth factor β and severe asthma: A perfect storm. Respir Med. 108:1409–1423. 2014. View Article : Google Scholar : PubMed/NCBI
15	Massagué J, Seoane J and Wotton D: Smad transcription factors. Genes Dev. 19:2783–2810. 2005. View Article : Google Scholar : PubMed/NCBI
16	Heldin CH and Moustakas A: Role of Smads in TGFβ signaling. Cell Tissue Res. 347:21–36. 2012. View Article : Google Scholar : PubMed/NCBI
17	Takagaki A, Otani S and Nanjo F: Antioxidative activity of microbial metabolites of (−)-epigallocatechin gallate produced in rat intestines. Biosci Biotechnol Biochem. 75:582–585. 2011. View Article : Google Scholar : PubMed/NCBI
18	Johnson MK and Loo G: Effects of epigallocatechin gallate and quercetin on oxidative damage to cellular DNA. Mutat Res. 459:211–218. 2000. View Article : Google Scholar : PubMed/NCBI
19	Gao Z, Han Y, Hu Y, Wu X, Wang Y, Zhang X, Fu J, Zou X, Zhang J, Chen X, et al: Targeting HO-1 by epigallocatechin-3-gallate reduces contrast-induced renal injury via anti-oxidative stress and anti-inflammation pathways. PLoS One. 11:e01490322016. View Article : Google Scholar : PubMed/NCBI
20	Ohno A, Kataoka S, Ishii Y, Terasaki T, Kiso M, Okubo M, Yamaguchi K and Tateda K: Evaluation of Camellia sinensis catechins as a swine antimicrobial feed additive that does not cause antibiotic resistance. Microbes Environ. 28:81–86. 2013. View Article : Google Scholar : PubMed/NCBI
21	Min KJ and Kwon TK: Anticancer effects and molecular mechanisms of epigallocatechin-3-gallate. Integr Med Res. 3:16–24. 2014. View Article : Google Scholar : PubMed/NCBI
22	Bitzer ZT, Elias RJ, Vijay-Kumar M and Lambert JD: (−)-Epigallocatechin-3-gallate decreases colonic inflammation and permeability in a mouse model of colitis, but reduces macronutrient digestion and exacerbates weight loss. Mol Nutr Food Res. 60:2267–2274. 2016. View Article : Google Scholar : PubMed/NCBI
23	Wu D, Wang J, Pae M and Meydani SN: Green tea EGCG, T cells and T cell-mediated autoimmune diseases. Mol Aspects Med. 33:107–118. 2012. View Article : Google Scholar : PubMed/NCBI
24	Haque A, Rahman MA, Chen ZG, Saba NF, Khuri FR, Shin DM and Amin Ruhul AR: Combination of erlotinib and EGCG induces apoptosis of head and neck cancers through posttranscriptional regulation of Bim and Bcl-2. Apoptosis. 20:986–995. 2015. View Article : Google Scholar : PubMed/NCBI
25	Funston W and Higgins B: Improving the management of asthma in adults in primary care. Practitioner. 258:15–19. 2014.PubMed/NCBI
26	Chakrawarti L, Agrawal R, Dang S, Gupta S and Gabrani R: Therapeutic effects of EGCG: A patent review. Expert Opin Ther Pat. 26:907–916. 2016. View Article : Google Scholar : PubMed/NCBI
27	Intra J and Kuo SM: Physiological levels of tea catechins increase cellular lipid antioxidant activity of vitamin C and vitamin E in human intestinal caco-2 cells. Chem Biol Interact. 169:91–99. 2007. View Article : Google Scholar : PubMed/NCBI
28	Yamagata K, Tanaka N and Suzuki K: Epigallocatechin 3-gallate inhibits 7-ketocholesterol-induced monocyte-endothelial cell adhesion. Microvasc Res. 88:25–31. 2013. View Article : Google Scholar : PubMed/NCBI
29	Inoue T, Suzuki Y and Ra C: Epigallocatechin-3-gallate induces cytokine production in mast cells by stimulating an extracellular superoxide-mediated calcium influx. Biochem Pharmacol. 82:1930–1939. 2011. View Article : Google Scholar : PubMed/NCBI
30	Shi J, Deng H, Pan H, Xu Y and Zhang M: Epigallocatechin-3-gallate attenuates microcystin-LR induced oxidative stress and inflammation in human umbilical vein endothelial cells. Chemosphere. 168:25–31. 2017. View Article : Google Scholar : PubMed/NCBI
31	Yu NH, Pei H, Huang YP and Li YF: (−)-Epigallocatechin-3-gallate inhibits arsenic-induced inflammation and apoptosis through suppression of oxidative stress in mice. Cell Physiol Biochem. 41:1788–1800. 2017. View Article : Google Scholar : PubMed/NCBI
32	Bakr SI, Mahran MZ and Soliman DA: Role of regulatory CD4⁺CD25⁺ Foxp3 T cells in bronchial asthma in Egyptian children. Egypt J Immunol. 20:29–38. 2013.PubMed/NCBI
33	Corrigan CJ and Kay AB: Asthma. Role of T-lymphocytes and lymphokines. Br Med Bull. 48:72–84. 1992. View Article : Google Scholar : PubMed/NCBI
34	Maddur MS, Miossec P, Kaveri SV and Bayry J: Th17 cells: Biology, pathogenesis of autoimmune and inflammatory diseases and therapeutic strategies. Am J Pathol. 181:8–18. 2012. View Article : Google Scholar : PubMed/NCBI
35	Palomares O: The role of regulatory T cells in IgE-mediated food allergy. J Investig Allergol Clin Immunol. 23:371–382. 2013.PubMed/NCBI
36	Ierodiakonou D, Postma DS, Koppelman GH, Gerritsen J, ten Hacken NH, Timens W, Boezen HM and Vonk JM: TGF-β1 polymorphisms and asthma severity, airway inflammation, and remodeling. J Allergy Clin Immunol. 131:582–585. 2013. View Article : Google Scholar : PubMed/NCBI
37	Halwani R, Al-Muhsen S, Al-Jahdali H and Hamid Q: Role of transforming growth factor-β in airway remodeling in asthma. Am J Respir Cell Mol Biol. 44:127–133. 2011. View Article : Google Scholar : PubMed/NCBI
38	Kamato D, Burch ML, Piva TJ, Rezaei HB, Rostam MA, Xu S, Zheng W, Little PJ and Osman N: Transforming growth factor-beta signalling: Role and consequences of Smad linker region phosphorylation. Cell Signal. 25:2017–2024. 2013. View Article : Google Scholar : PubMed/NCBI
39	Liu X, Yang Y, Zhang X, Xu S, He S, Huang W and Roberts MS: Compound Astragalus and Salvia miltiorrhiza extract inhibits cell invasion by modulating transforming growth factor-beta/Smad in HepG2 cell. J Gastroenterol Hepatol. 25:420–426. 2010. View Article : Google Scholar : PubMed/NCBI
40	McMillan SJ, Xanthou G and Lloyd CM: Manipulation of allergen-induced airway remodeling by treatment with anti-TGF-beta antibody: Effect on the Smad signaling pathway. J Immunol. 174:5774–5780. 2005. View Article : Google Scholar : PubMed/NCBI