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TNF-α mRNA Expression Correlates with TGF-β mRNA Expression In Vivo

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Abstract

TNF-α is postulated to play a significant role in regulating TGF-β1 expression. In lung fibroblasts, for example, TNF-α is supposed to induce TGF-β1 via AP-1 activation. TNF-α receptor, knock-out mice are resistant to induced fibrosis and over-expression of TNF-α causes increased TGF-β1 production in mice. Therefore, we investigated whether TNF-α mRNA levels are associated with the TGF-β1 mRNA levels of blood leucocytes in humans. Quantitative real-time PCR of TNF-α and TGF-β1 was performed in 118 Germans. Calculations of expression were made with the 2−ΔΔCT method. When the investigated population was divided in two groups (TNF-α low and TNF-α high) by the median of the determined TNF-α expression, highly significant (p < 0.0001) differences of TGF-β1 mRNA expression were revealed. Additionally, dividing the investigated population into quartiles of the determined TNF-α expression showed significantly different TGF-β1 mRNA expressions. Comparing the determined CT-values of TNF-α in context with these of TGF-β1, a coefficient of determination R 2 = 0.4635 was calculated. In this study we demonstrated in vivo a significant association of the relative TNF-α/B2M mRNA expression and the relative TGF-β1/B2M mRNA expression in 118 Germans.

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References

  1. Bartram, U., and C.P. Speer. 2004. The role of transforming growth factor beta in lung development and disease. Chest 125: 754–765.

    Article  PubMed  Google Scholar 

  2. Sime, P.J., and K.M. O'Reilly. 2001. Fibrosis of the lung and other tissues: New concepts in pathogenesis and treatment. Clinical Immunology 99: 308–319.

    Article  PubMed  CAS  Google Scholar 

  3. Selman, M., V.J. Thannickal, A. Pardo, D.A. Zisman, F.J. Martinez, and J.P. Lynch 3rd. 2004. Idiopathic pulmonary fibrosis: Pathogenesis and therapeutic approaches. Drugs 64: 405–430.

    Article  PubMed  CAS  Google Scholar 

  4. Samad, F., K.T. Uysal, S.M. Wiesbrock, M. Pandey, G.S. Hotamisligil, and D.J. Loskutoff. 1999. Tumor necrosis factor alpha is a key component in the obesity-linked elevation of plasminogen activator inhibitor 1. Proceedings of the National Academy of Sciences of the United States of America 96: 6902–6907.

    Article  PubMed  CAS  Google Scholar 

  5. Warshamana, G.S., M. Corti, and A.R. Brody. 2001. TNF-alpha, PDGF, and TGF-beta(1) expression by primary mouse bronchiolar-alveolar epithelial and mesenchymal cells: tnf-alpha induces TGF-beta(1). Experimental and Molecular Pathology 71: 13–33.

    Article  PubMed  CAS  Google Scholar 

  6. Phillips, A.O., N. Topley, R. Steadman, K. Morrisey, and J.D. Williams. 1996. Induction of TGF-beta 1 synthesis in D-glucose primed human proximal tubular cells by IL-1 beta and TNF alpha. Kidney International 50: 1546–1554.

    Article  PubMed  CAS  Google Scholar 

  7. Phan, S.H., M. Gharaee-Kermani, B. McGarry, S.L. Kunkel, and F.W. Wolber. 1992. Regulation of rat pulmonary artery endothelial cell transforming growth factor-beta production by IL-1 beta and tumor necrosis factor-alpha. Journal of Immunology 149: 103–106.

    CAS  Google Scholar 

  8. Sullivan, D.E., M. Ferris, D. Pociask, and A.R. Brody. 2008. The latent form of TGFbeta(1) is induced by TNFalpha through an ERK specific pathway and is activated by asbestos-derived reactive oxygen species in vitro and in vivo. Journal of Immunotoxicology 5: 145–149.

    Article  PubMed  CAS  Google Scholar 

  9. Sullivan, D.E., M. Ferris, H. Nguyen, E. Abboud, and A.R. Brody. 2009. TNF-alpha induces TGF-beta1 expression in lung fibroblasts at the transcriptional level via AP-1 activation. Journal of Cellular and Molecular Medicine 13: 1866–1876.

    Article  PubMed  Google Scholar 

  10. Helmig, S., B. Hadzaad, J. Dohrel, and J. Schneider. 2009. Influence of the Cyp1B1 L432V gene polymorphism and exposure to tobacco smoke on Cyp1B1 mRNA expression in human leukocytes. Drug Metabolism and Disposition 37: 1490–1495.

    Article  PubMed  CAS  Google Scholar 

  11. Vandesompele, J., K. De Preter, F. Pattyn, B. Poppe, N. Van Roy, A. De Paepe, and F. 2002. Speleman: Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes. Genome Biology 3:RESEARCH0034.

  12. Pfaffl, M.W. 2001. A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Research 29: e45.

    Article  PubMed  CAS  Google Scholar 

  13. Nakamura, Y., R. Kano, A. Hasegawa, and S. Watanabe. 2002. Interleukin-8 and tumor necrosis factor alpha production in human epidermal keratinocytes induced by Trichophyton mentagrophytes. Clinical and Diagnostic Laboratory Immunology 9: 935–937.

    PubMed  CAS  Google Scholar 

  14. Zhang, X., L. Ding, and A.J. Sandford. 2005. Selection of reference genes for gene expression studies in human neutrophils by real-time PCR. BMC Molecular Biology 6: 4.

    Article  PubMed  Google Scholar 

  15. Kim, S.J., A. Glick, M.B. Sporn, and A.B. Roberts. 1989. Characterization of the promoter region of the human transforming growth factor-beta 1 gene. The Journal of Biological Chemistry 264: 402–408.

    PubMed  CAS  Google Scholar 

  16. Geiser, A.G., S.J. Kim, A.B. Roberts, and M.B. Sporn. 1991. Characterization of the mouse transforming growth factor-beta 1 promoter and activation by the Ha-ras oncogene. Molecular and Cellular Biology 11: 84–92.

    PubMed  CAS  Google Scholar 

  17. Blobe, G.C., W.P. Schiemann, and H.F. Lodish. 2000. Role of transforming growth factor beta in human disease. The New England Journal of Medicine 342: 1350–1358.

    Article  PubMed  CAS  Google Scholar 

  18. Helmig, S., A. Belwe, and J. Schneider. 2009. Association of transforming growth factor beta1 gene polymorphisms and asbestos-induced fibrosis and tumors. Journal of Investigative Medicine 57: 655–661.

    PubMed  CAS  Google Scholar 

  19. Helmig, S., N. Aliahmadi, and J. Schneider. 2010. TNF-α gene polymorphisms in asbestos induced diseases. Biomarkers. ahead of print

  20. Sime, P.J., R.A. Marr, D. Gauldie, Z. Xing, B.R. Hewlett, F.L. Graham, and J. Gauldie. 1998. Transfer of tumor necrosis factor-alpha to rat lung induces severe pulmonary inflammation and patchy interstitial fibrogenesis with induction of transforming growth factor-beta1 and myofibroblasts. The American Journal of Pathology 153: 825–832.

    Article  PubMed  CAS  Google Scholar 

  21. Liu, J.Y., and A.R. Brody. 2001. Increased TGF-beta1 in the lungs of asbestos-exposed rats and mice: Reduced expression in TNF-alpha receptor knockout mice. Journal of Environmental Pathology, Toxicology and Oncology 20: 97–108.

    PubMed  CAS  Google Scholar 

  22. Liu, J.Y., D.M. Brass, G.W. Hoyle, and A.R. Brody. 1998. TNF-alpha receptor knockout mice are protected from the fibroproliferative effects of inhaled asbestos fibers. The American Journal of Pathology 153: 1839–1847.

    Article  PubMed  CAS  Google Scholar 

  23. Grattendick, K.J., J.M. Nakashima, L. Feng, S.N. Giri, and S.B. Margolin. 2008. Effects of three anti-TNF-alpha drugs: etanercept, infliximab and pirfenidone on release of TNF-alpha in medium and TNF-alpha associated with the cell in vitro. International Immunopharmacology 8: 679–687.

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Institut und Poliklinik für Arbeits- und Sozialmedizin, Justus-Liebig-Universität, Aulweg 129, 35392, Giessen, Germany

    Simone Helmig, Peter Stephan, Juliane Döhrel & Joachim Schneider

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  1. Simone Helmig
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  2. Peter Stephan
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  3. Juliane Döhrel
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  4. Joachim Schneider
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Correspondence to Simone Helmig.

Additional information

Some of the results are included in the thesis of P. Stephan

Dedicated to Prof. Woitowitz on occasion of his 75th birthday

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Helmig, S., Stephan, P., Döhrel, J. et al. TNF-α mRNA Expression Correlates with TGF-β mRNA Expression In Vivo . Inflammation 34, 255–259 (2011). https://doi.org/10.1007/s10753-010-9231-2

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  • DOI: https://doi.org/10.1007/s10753-010-9231-2

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