Skip to main content
Log in

N-acetylcysteine inhibits IL-8 and MMP-9 release and ICAM-1 expression by bronchoalveolar cells from interstitial lung disease patients

  • Published:
Pharmacological Reports Aims and scope Submit manuscript

Abstract

N-acetylcysteine (NAC), owing to its antioxidant, mucolytic and anti-inflammatory properties, is used in the treatment of various pulmonary disorders. However, the direct effects of NAC on bronchoalveolar lavage (BAL) cells from patients suffering from interstitial lung diseases have not yet been studied. Therefore, the aim of the present work was to evaluate the effect of NAC on interleukin-8 (IL-8) and matrix metalloproteinase-9 (MMP-9) production as well as intercellular cell adhesion molecule-1 (ICAM-1) expression byBALcells from interstitial lung diseases. The study was performed on BALcells from nine patients with interstitial lung disease: four patients with idiopathic pulmonary fibrosis (IPF) and five patients with sarcoidosis. Cultured unstimu-lated BAL cells were treated with increasing doses of NAC (1-30 mM). Production of IL-8 and MMP-9 was evaluated by specific enzyme-linked immuno-sorbent assays and ICAM-1 expression was studied by immunohistochemistry. NAC exerted a dose-dependent inhibitory effectonIL-8 and MMP-9 release and ICAM- expression byBALmacrophages and lymphocytes from patients with IPF and sarcoidosis. In conclusion, NAC inhibits production of factors playing a key role in the etiopathogenesis of interstitial lung diseases, thus suggesting its possible therapeutic potency in the treatment of these disorders.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

Abbreviations

BAL:

bronchoalveolar lavage

ELISA:

enzyme-linked immunosorbent assay

ICAM-1:

intercellular cell adhesion molecule-1

IL:

interleukin

IPF:

idiopathic pulmonary fibrosis

Lym:

lymphocytes

Mac:

macrophages

MMP-9:

matrix metalloproteinase-9

NAC:

iV-acetylcysteine

NF-KB:

nuclear factor kappa B

TNF:

tumor necrosis factor

VCAM-1:

vascular cell adhesion molecule

References

  1. American Thoracic Society/European Respiratory Society international multidisciplinary consensus classification of the idiopathic interstitial pneumonias. This joint statement of the American Thoracic Society (ATS) and the European Respiratory Society (ERS) was adopted by the ATS board of directors, June 2001 and by ERS Executive Comittee, June 2001. Am J Respir Crit Care Med, 2002, 165, 277–304.

    Article  Google Scholar 

  2. Antoniou KM, Tzouvelekis A, Alexandrakis MG, Sfiridaki K, Tsiligiani I, Rachiotis G, Tzanakis N et al.: Different angiogenic activity in pulmonary sarcoidosis and idiopathic pulmonary fibrosis. Chest, 2006, 130, 982–988.

    Article  Google Scholar 

  3. Ask K, Martin G, Kolb M, Gauldie J: Targeting genes for treatment in idiopathic pulmonary fibrosis. Proc Am Thor Soc, 2006, 3, 389–393.

    Article  CAS  Google Scholar 

  4. Atkinson JJ, Senior RM: Matrix metalloproteinase-9 in lung remodeling. Am J Respir Cell Mol Biol, 2003, 28, 12–14.

    Article  CAS  Google Scholar 

  5. Behr J: Novel aspects of treatment for interstitial lung diseases. In: Diffuse Parenchymal Lung Disease. Eds. Costabel U, du Bois RM JJ, Prog Respir Res Basel, Karger, 2007, 36, 117–126.

    Article  Google Scholar 

  6. Car BD, Meloni F, Luisetti M, Semenzato G, Gialdroni-Grassi G, Waltz A: Elevated IL-8 and MCP-1 in the bronchoalveolar lavage fluid of patients with idiopathic pulmonary fibrosis and pulmonary sarcoidosis. Am J Respir Crit Care Med, 1994, 149, 655–659.

    Article  CAS  Google Scholar 

  7. Dekhuijzen PRN: Antioxidant properties of N-acetylcysteine: their relevance in relation to chronic obstructive pulmonary disease. Eur Respir J, 2004, 23, 629–636.

    Article  CAS  Google Scholar 

  8. Demedts M, Behr J, Buhl R, Costabel U, Dekhuijzen R, Jansen HM, MacNee W et al.: IFIGENIA Study Group: High-dose acetylcysteine in idiopathic pulmonary fibrosis. N Engl J Med, 2005, 353, 22292–22242.

    Article  Google Scholar 

  9. Girgis RE, Basha MA, Maliarik M: Cytokines in bron-choalveolar lavage fluid of patients with active pulmonary sarcoidosis. Am J Respir Crit Care Med, 1995, 152, 71–75.

    Article  CAS  Google Scholar 

  10. Henry MT, McMahon K, Mackarel AJ, Prikk K, Sorsa T, Maisi P, Sepper R et al.: Matrix metalloproteinases and tissue inhibitor of metalloproteinase-1 in sarcoidosis and IPF. Eur Respir J, 2002, 20, 1220–1227.

    Article  CAS  Google Scholar 

  11. Hunninghake GW: Antioxidant therapy for idiopathic pulmonary fibrosis. N Engl J Med, 2005, 353, 2285–2287.

    Article  CAS  Google Scholar 

  12. Ishii Y, Kitamura S: Elevated level of soluble ICAM in serum and BAL fluid in patients with active sarcoidosis. Chest, 1995, 107, 1636–1640.

    Article  CAS  Google Scholar 

  13. John M, Oltmans U, Fietze I, Witt C, Jung K: Increased production of matrix metalloproteinase-2 in alveolar macrophages and regulation by interleukin-10 in patients with acute pulmonary sarcoidosis. Exp Lung Res, 2002, 28, 55–68.

    Article  CAS  Google Scholar 

  14. Kim KA, Lim YS, Kim KM, Yoon JH, Lee HS: 15d-De-oxy-A12,14 -prostaglandin J2 modulates collagen type I synthesis in human hepatic stellate cells by inducing oxidative stress. Prostaglandins Leukot Essent Fatty Acids, 2005, 73, 361–367.

    Article  CAS  Google Scholar 

  15. Kinula VL, Fattman ChL, Tan RJ, Oury TD: Oxidative stress in pulmonary fibrosis. Am J Respir Crit Care Med, 2005, 172, 417–422.

    Article  Google Scholar 

  16. Lagente V, Manoury B, Nenan S, Le Quement C, Martin-Chouly C, Boichot E: Role of matrix metalloproteinases in the development of airway inflammation and remodeling. Brazil J Med Biol Res, 2005, 38, 1521–1530.

    Article  CAS  Google Scholar 

  17. Lappas M, Permezel M, Rice G: N-acetylcysteine inhibits phospholipid metabolizm, proinflammatory cytokine release, protease activity, and nuclear factor-KB deoxyribonucleic acid-binding acivity in human fetal membranes in vitro. J Clin Endocrinol Metabol, 2003, 88, 1723–1729.

    Article  CAS  Google Scholar 

  18. Maher TM, Wells AU, Laurent GJ: Idiopathic pulmonary fibrosis: multiple causes and multiple mechanisms? Eur Resp J, 2007, 30, 835–839.

    Article  CAS  Google Scholar 

  19. Paterson RL, Galley HF, Webster NR: Te effect of of N-acetylcysteine on nuclear factor-κB activation, interleukin-6, interleukin-8 and intercellular adhesion molecule-1 expression in patients with sepsis. Crit Care Med, 2003, 31, 2574–2578.

    Article  CAS  Google Scholar 

  20. Radomska-Leśniewska DM, Sadowska AM, van Over-veld FJ, Demkow U, Zieliński J, De Backer WA: Influence of N-acetylcysteine on ICAM-1 expression and IL-8 release from endothelial and epithelial cells. J Physiol Pharmacol, 2006, 57, 325–334.

    PubMed  Google Scholar 

  21. Radomska-Leśniewska DM, Sobiecka M, Choros-towska-Wynimko J, Białas-Chromiec B, Kuś J, Wesołowski S, Skopińska-Różewska E: Relationship between IL-8, IL-10, and MMP-9 level and morphological pattern of BAL fluid in interstitial lung diseases patients. Centr Eur J Immunol, 2003, 28, 155–159.

    Google Scholar 

  22. Roman J, Galis Z: Sarkoidosis: a mystery tale of inflammation, tissue remodeling and matrix metalloproteinases. Hum Pathol, 2002, 33, 1155–1157.

    Article  Google Scholar 

  23. Sadowska AM, Manuel-Y-Keenoy B, De Backer WA: Antioxidant and anti-inflammatory efficacy of NAC in the treatment of COPD: discordant in vitro and in vivo dose-effects: a review. Pulm Pharmacol Ther, 2007, 20, 9–22.

    Article  CAS  Google Scholar 

  24. Silvestri M, Serpero L, Petecchia L, Sabatini F, Cerasoli F Jr, Rossi GA: Cytokine-activated bronchial epithelial cell pro-inflammatory functions are downregulated in vitro by ciclesonide. Pulm Pharmacol Ther, 2006, 19, 210–217.

    Article  CAS  Google Scholar 

  25. Sukurada S, Kato T, Okamoto T: Induction of cytokines and ICAM-1 by proinflammatory cytokines i primary rheumatoid synovial fibroblasts and inhibition by N-acetyl-L-cysteine and aspirin. Intern Immunol, 1996, 8, 1483–1493.

    Article  Google Scholar 

  26. Tong, Z, Dai H, Chen B, Abdoch Z, Guzman J, Costabel U: Inhibition of cytokine release from alveolar macro-phages in pulmonary sarcoidosis by pentoxifylline: comparison with dexamethasone. Chest, 2003, 124, 1526–1532.

    Article  CAS  Google Scholar 

  27. Vasallo R: Recent advances in interstitial lung diseases research. Malta Med J, 2006, 18, 12–17.

    Google Scholar 

  28. Walter N, Cllard HR, Kig TE Jr: Current perspectives on the treatment of idiopathic pulmonary fibrosis. Proc Am Thor Soc, 2006, 3, 330–338.

    Article  CAS  Google Scholar 

  29. Wuyts WA, Vanaudenaerde BM, Dupond LJ, Demets MG, Verleden GM: N-acetylcysteine reduced chemokine released via inhibition of p38 MAPK in human airway smooth muscle cell. Eur Respir J, 2003, 22, 43–49.

    Article  CAS  Google Scholar 

  30. Ye Q, Chen B, Tong Z, Nakamura S, Sarria R, Costabel U, Guzman J: Thalidomide reduces IL-18, IL-8 and TNF-α release from alveolar macrophages in inerstitial lung disease. Eur Respir J, 2006, 28, 824–831.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Dorota M. Radomska-Leśniewska.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Radomska-Leśniewska, D.M., Skopińska-Różewska, E., Jankowska-Steifer, E. et al. N-acetylcysteine inhibits IL-8 and MMP-9 release and ICAM-1 expression by bronchoalveolar cells from interstitial lung disease patients. Pharmacol. Rep 62, 131–138 (2010). https://doi.org/10.1016/S1734-1140(10)70250-4

Download citation

  • Received:

  • Revised:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1016/S1734-1140(10)70250-4

Key words

Navigation