Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
International Journal of Molecular Medicine
Join Editorial Board Propose a Special Issue
Print ISSN: 1107-3756 Online ISSN: 1791-244X
Journal Cover
April-2021 Volume 47 Issue 4

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
April-2021 Volume 47 Issue 4

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML

  • Supplementary Files
    • Supplementary_Data.pdf
Article

Curcumin protects BEAS‑2B cells from PM2.5‑induced oxidative stress and inflammation by activating NRF2/antioxidant response element pathways

  • Authors:
    • Shuo Yang
    • Xiao-Long Huang
    • Jin Chen
    • Li-Na Mao
    • Xu Liu
    • Wen-Sheng Yuan
    • Xiao-Jie Wu
    • Guang-Wei Luo
  • View Affiliations / Copyright

    Affiliations: Department of Pulmonary and Critical Care Medicine, Wuhan No. 1 Hospital, Wuhan, Hubei 430000, P.R. China
  • Article Number: 45
    |
    Published online on: February 8, 2021
       https://doi.org/10.3892/ijmm.2021.4878
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

Fine particulate matter (PM2.5) with an average aerodynamic diameter of <2.5 µm can cause severe lung injury. Oxidative stress and inflammation are considered the main outcomes of PM2.5 exposure. Curcumin is a well‑known antioxidant; however, its effect on PM2.5‑induced oxidative injury in airway epithelial cells remains unclear. In the present study, it was demonstrated that pre‑treatment with curcumin significantly reduced the PM2.5‑induced apoptosis of BEAS‑2B human bronchial epithelial cells by decreasing the level of intercellular reactive oxygen species. Western blot analysis revealed that curcumin increased the expression of nuclear factor erythroid 2‑related factor 2 (NRF2) and regulated the transcription of downstream genes, particularly those encoding antioxidant enzymes. Moreover, curcumin reduced the PM2.5‑induced expression and production of inflammatory factors, and induced the expression of the anti‑inflammatory factors, interleukin (IL)‑5 and IL‑13. Taken together, the present study demonstrates that curcumin protects BEAS‑2B cells against PM2.5‑induced oxidative damage and inflammation, and prevents cell apoptosis by increasing the activation of NRF2‑related pathways. It is thus suggested that curcumin may be a potential compound for use in the prevention of PM2.5‑induced tissue injury.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

View References

1 

Huff RD, Carlsten C and Hirota JA: An update on immunologic mechanisms in the respiratory mucosa in response to air pollutants. J Allergy Clin Immunol. 143:1989–2001. 2019. View Article : Google Scholar : PubMed/NCBI

2 

Li N, Alam J, Venkatesan MI, Eiguren FA, Schmitz D, Di SE, Slaughter N, Killeen E, Wang X, Huang A, et al: Nrf2 is a key transcription factor that regulates antioxidant defense in macrophages and epithelial cells: Protecting against the proinflammatory and oxidizing effects of diesel exhaust chemicals. J Immunol. 173:3467–3481. 2004. View Article : Google Scholar : PubMed/NCBI

3 

Georas SN and Rezaee F: Epithelial barrier function: At the front line of asthma immunology and allergic airway inflammation. J Allergy Clin Immunol. 134:509–520. 2014. View Article : Google Scholar : PubMed/NCBI

4 

Guan L, Rui W, Bai R, Zhang W, Zhang F and Ding W: Effects of size-fractionated particulate matter on cellular oxidant radical generation in human bronchial epithelial BEAS-2B cells. Int J Environ Res Public Health. 13:4832016. View Article : Google Scholar :

5 

Leclercq B, Kluza J, Antherieu S, Sotty J, Alleman LY, Perdrix E, Loyens A, Coddeville P, Lo Guidice JM, Marchetti P and Garçon G: Air pollution-derived PM2.5 impairs mitochondrial function in healthy and chronic obstructive pulmonary diseased human bronchial epithelial cells. Environ Pollut. 243:1434–1449. 2018. View Article : Google Scholar : PubMed/NCBI

6 

Raudoniute J, Stasiulaitiene I, Kulvinskiene I, Bagdonas E, Garbaras A, Krugly E, Martuzevicius D, Bironaite D and Aldonyte R: Pro-inflammatory effects of extracted urban fine particulate matter on human bronchial epithelial cells BEAS-2B. Environ Sci Pollut Res Int. 25:32277–32291. 2018. View Article : Google Scholar : PubMed/NCBI

7 

Gong P, Hu B, Stewart D, Ellerbe M, Figueroa YG, Blank V, Beckman BS and Alam J: Cobalt induces heme oxygenase-1 expression by a hypoxia-inducible factor-independent mechanism in Chinese hamster ovary cells: Regulation by Nrf2 and MafG transcription factors. J Biol Chem. 276:27018–27025. 2001. View Article : Google Scholar : PubMed/NCBI

8 

Xu MX, Zhu YF, Chang HF and Liang Y: Nanoceria restrains PM2.5-induced metabolic disorder and hypothalamus inflammation by inhibition of astrocytes activation related NF-κB pathway in Nrf2 deficient mice. Free Radic Biol Med. 99:259–272. 2016. View Article : Google Scholar : PubMed/NCBI

9 

Motterlini R, Foresti R, Bassi R and Green CJ: Curcumin, an anti-oxidant and anti-inflammatory agent, induces heme oxygenase-1 and protects endothelial cells against oxidative stress. Free Radic Biol Med. 28:1303–1312. 2000. View Article : Google Scholar : PubMed/NCBI

10 

Fetoni AR, Paciello F, Mezzogori D, Rolesi R, Eramo SL, Paludetti G and Troiani D: Molecular targets for anticancer redox chemotherapy and cisplatin-induced ototoxicity: The role of curcumin on pSTAT3 and Nrf-2 signalling. Br J Cancer. 113:1434–1444. 2015. View Article : Google Scholar : PubMed/NCBI

11 

Qi Ni, Zeng SE, Tan N, Huang LZ, Cheng QY and Zhang MY: Effect of curcumin on proliferation of hepatocellular carcinoma Hep1 cells and expression of HIF-1α mRNA in normal oxygen conditions. Liaoning Tra Chin Med. 8:21–23. 2010.

12 

Song XJ, Zhou HY, Sun YX and Huang HC: Inhibitory effects of curcumin on H2O2-induced cell damage and APP expression and processing in SH-SY5Y cells transfected with APP gene with Swedish mutation. Mol Biol Rep. 47:2047–2059. 2020. View Article : Google Scholar : PubMed/NCBI

13 

Woods CG, Fu J, Xue P, Hou Y, Pluta LJ, Yang L, Zhang Q, Thomas RS, Andersen ME and Pi J: Dose-dependent transitions in Nrf2-mediated adaptive response and related stress responses to hypochlorous acid in mouse macrophages. Toxicol Appl Pharmacol. 238:27–36. 2009. View Article : Google Scholar : PubMed/NCBI

14 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar

15 

Suo D, Zeng S, Zhang J, Meng L and Weng L: PM2.5 induces apoptosis, oxidative stress injury and melanin metabolic disorder in human melanocytes. Exp Ther Med. 19:3227–3238. 2020.PubMed/NCBI

16 

Li X, Ding Z, Zhang C, Zhang X, Meng Q, Wu S, Wang S, Yin L, Pu Y and Chen R: MicroRNA-1228(*) inhibit apoptosis in A549 cells exposed to fine particulate matter. Environ Sci Pollut Res Int. 23:10103–10113. 2016. View Article : Google Scholar : PubMed/NCBI

17 

Li N and Nel AE: Role of the Nrf2-mediated signaling pathway as a negative regulator of inflammation: Implications for the impact of particulate pollutants on asthma. Antioxid Redox Signal. 8:88–98. 2006. View Article : Google Scholar : PubMed/NCBI

18 

Wang LF, Su SW, Wang L, Zhang GQ, Zhang R, Niu YJ, Guo YS, Li CY, Jiang WB, Liu Y and Guo HC: Tert-butylhydroquinone ameliorates doxorubicin-induced cardiotoxicity by activating Nrf2 and inducing the expression of its target genes. Am J Transl Res. 7:1724–35. 2015.PubMed/NCBI

19 

Block ML and Calderón-Garcidueñas L: Air pollution: Mechanisms of neuroinflammation and CNS disease. Trends Neurosci. 32:506–516. 2009. View Article : Google Scholar : PubMed/NCBI

20 

Zhang S, Jiao Y, Li C, Liang X, Jia H, Nie Z and Zhang Y: Dimethyl itaconate alleviates the inflammatory responses of macrophages in sepsis. Inflammation. Oct 7–2020.Epub ahead of print. View Article : Google Scholar

21 

Jia H, Liu Y, Guo D, He W, Zhao L and Xia S: PM2.5-induced pulmonary inflammation via activating of the NLRP3/caspase-1 signaling pathway. Environ Toxicol. Sep 30–2020.Epub ahead of print.

22 

Ravanetti L, Dijkhuis A, Dekker T, Sabogal Pineros YS, Ravi A, Dierdorp BS, Erjefält JS, Mori M, Pavlidis S, Adcock IM, et al: IL-33 drives influenza-induced asthma exacerbations by halting innate and adaptive antiviral immunity. J Allergy Clin Immunol. 143:1355–1370.e16. 2019. View Article : Google Scholar

23 

Gorska K, Nejman-Gryz P, Paplinska-Goryca M, Korczynski P, Prochorec-Sobieszek M and Krenke R: Comparative study of IL-33 and IL-6 levels in different respiratory samples in mild-to-moderate asthma and COPD. COPD. 15:36–45. 2018. View Article : Google Scholar : PubMed/NCBI

24 

Chang SH, Reynolds JM, Pappu BP, Chen G, Martinez GJ and Dong C: Interleukin-17C promotes Th17 cell responses and autoimmune disease via interleukin-17 receptor E. Immunity. 35:611–621. 2011. View Article : Google Scholar : PubMed/NCBI

25 

Swaidani S, Bulek K, Kang Z, Liu C, Lu Y, Yin W, Aronica M and Li X: The critical role of epithelial-derived Act1 in IL-17- and IL-25-mediated pulmonary inflammation. J Immunol. 182:1631–1640. 2009. View Article : Google Scholar : PubMed/NCBI

26 

Bao ZJ, Fan YM, Cui YF, Sheng YF and Zhu M: Effect of PM2.5 mediated oxidative stress on the innate immune cellular response of Der p1 treated human bronchial epithelial cells. Eur Rev Med Pharmacol Sci. 21:2907–2912. 2017.PubMed/NCBI

27 

Keleku LN, Suzuki M and Yamamoto M: An overview of the advantages of KEAP1-NRF2 system activation during inflammatory disease treatment. Antioxid Redox Signal. 29:1746–1755. 2018. View Article : Google Scholar

28 

Menon VP and Sudheer AR: Antioxidant and anti-inflammatory properties of curcumin. Adv Exp Med Biol. 595:105–125. 2007. View Article : Google Scholar : PubMed/NCBI

29 

Merrell JG, McLaughlin SW, Tie L, Laurencin CT, Chen AF and Nair LS: Curcumin-loaded poly(epsilon-caprolactone) nanofibres: Diabetic wound dressing with anti-oxidant and anti-inflammatory properties. Clin Exp Pharmacol Physiol. 36:1149–1156. 2009. View Article : Google Scholar : PubMed/NCBI

30 

Yang X, Lv JN, Li H, Jiao B, Zhang QH, Zhang Y, Zhang J, Liu YQ, Zhang M, Shan H, et al: Curcumin reduces lung inflammation via Wnt/β-catenin signaling in mouse model of asthma. J Asthma. 54:335–340. 2017. View Article : Google Scholar

31 

Lin X, Bai D, Wei Z, Zhang Y, Huang Y, Deng H and Huang X: Curcumin attenuates oxidative stress in RAW264.7 cells by increasing the activity of antioxidant enzymes and activating the Nrf2-Keap1 pathway. PLoS One. 14:e02167112019. View Article : Google Scholar : PubMed/NCBI

32 

Zheng LZ, Chen LW, Hu XY, Lian J, Zhao GJ, Hong GL, Lu ZQ and Qiu QM: Curcumin upregitates mitochondrial fusion protein 2 to relieve acute lung injury in sepsis mice. Chin J Burns. 29:58–64. 2020.

33 

Qin K and Guo XJ: Research progress on the mechanism of curcumin in the treatment of chronic obstructive pulmonary disease. Chin J Respirat Cri Care. 19:99–103. 2020.

34 

Qin Z, Wang B, Tan ZX and Luo SH: Curcumin inhibits the TLR4/HMGB1 pathway to protect lipopolysaccharide from inducing acute lung injury. Chin J Clin Thor Cardiovasc Sur. 27:89–92. 2020.

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Yang S, Huang X, Chen J, Mao L, Liu X, Yuan W, Wu X and Luo G: Curcumin protects BEAS‑2B cells from PM<sub>2.5</sub>‑induced oxidative stress and inflammation by activating NRF2/antioxidant response element pathways. Int J Mol Med 47: 45, 2021.
APA
Yang, S., Huang, X., Chen, J., Mao, L., Liu, X., Yuan, W. ... Luo, G. (2021). Curcumin protects BEAS‑2B cells from PM<sub>2.5</sub>‑induced oxidative stress and inflammation by activating NRF2/antioxidant response element pathways. International Journal of Molecular Medicine, 47, 45. https://doi.org/10.3892/ijmm.2021.4878
MLA
Yang, S., Huang, X., Chen, J., Mao, L., Liu, X., Yuan, W., Wu, X., Luo, G."Curcumin protects BEAS‑2B cells from PM<sub>2.5</sub>‑induced oxidative stress and inflammation by activating NRF2/antioxidant response element pathways". International Journal of Molecular Medicine 47.4 (2021): 45.
Chicago
Yang, S., Huang, X., Chen, J., Mao, L., Liu, X., Yuan, W., Wu, X., Luo, G."Curcumin protects BEAS‑2B cells from PM<sub>2.5</sub>‑induced oxidative stress and inflammation by activating NRF2/antioxidant response element pathways". International Journal of Molecular Medicine 47, no. 4 (2021): 45. https://doi.org/10.3892/ijmm.2021.4878
Copy and paste a formatted citation
x
Spandidos Publications style
Yang S, Huang X, Chen J, Mao L, Liu X, Yuan W, Wu X and Luo G: Curcumin protects BEAS‑2B cells from PM<sub>2.5</sub>‑induced oxidative stress and inflammation by activating NRF2/antioxidant response element pathways. Int J Mol Med 47: 45, 2021.
APA
Yang, S., Huang, X., Chen, J., Mao, L., Liu, X., Yuan, W. ... Luo, G. (2021). Curcumin protects BEAS‑2B cells from PM<sub>2.5</sub>‑induced oxidative stress and inflammation by activating NRF2/antioxidant response element pathways. International Journal of Molecular Medicine, 47, 45. https://doi.org/10.3892/ijmm.2021.4878
MLA
Yang, S., Huang, X., Chen, J., Mao, L., Liu, X., Yuan, W., Wu, X., Luo, G."Curcumin protects BEAS‑2B cells from PM<sub>2.5</sub>‑induced oxidative stress and inflammation by activating NRF2/antioxidant response element pathways". International Journal of Molecular Medicine 47.4 (2021): 45.
Chicago
Yang, S., Huang, X., Chen, J., Mao, L., Liu, X., Yuan, W., Wu, X., Luo, G."Curcumin protects BEAS‑2B cells from PM<sub>2.5</sub>‑induced oxidative stress and inflammation by activating NRF2/antioxidant response element pathways". International Journal of Molecular Medicine 47, no. 4 (2021): 45. https://doi.org/10.3892/ijmm.2021.4878
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team