Skip to main content

Advertisement

Log in

Effects of Sulfur Dioxide on the Expressions of EGF, EGFR, and COX-2 in Airway of Asthmatic Rats

  • Published:
Archives of Environmental Contamination and Toxicology Aims and scope Submit manuscript

Abstract

The pathogenesis of asthma involves a combination of genetic and environmental factors. The epidemiology studies have shown that SO2 might play an important role in the initiation or exacerbation of the asthma disease. To investigate the asthmatic molecular mechanisms exposed to SO2, male Wistar rats were divided randomly into four equal groups of six animals each: (1) SO2 group, (2) ovalbumin (OVA) group (asthma group), (3) SO2 plus OVA group, and (4) control group. The rats were challenged by ovalbumin (OVA) or SO2 (5.6 mg/m3) inhalation alone or together. The mRNA and protein levels of asthma-related genes (EGF, EGFR, and COX-2) were analyzed in lungs and tracheas using real-time reverse transcription–polymerase chain reaction assay, radioimmunoassay method, and Western blot analysis, respectively. The results showed that inhaled SO2 alone increased the mRNA and protein expressions of three tested genes in lung and trachea tissues, but only the mRNA levels of EGFR and COX-2 in tracheas were significantly increased compared with the control. However, OVA exposure significantly induced the mRNA and protein expressions of EGF, EGFR, and COX-2 compared with the control. Meanwhile, OVA plus SO2 inhalation enhanced the mRNA and protein levels of these genes in rat airways, versus exposure to OVA alone. These results suggested that SO2 could increase the expressions of EGF, EGFR, and COX-2 on the transcription and translation levels in the lungs and tracheas from asthmatic rats, which might be one of the possible mechanisms by which SO2 pollution aggravates asthma disease.

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

Access this article

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

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

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  • Amishima M, Munakata M, Nasuhara Y, Sato A, Takashi T, Homma Y, Kawakami Y (1998) Expression of epidermal growth factor and epidermal growth factor receptor immunoreactivity in the asthmatic human airway. Am J Respir Crit Care Med 157:1907–1912

    CAS  Google Scholar 

  • Bai J, Meng Z (2005) Effects of sulfur dioxide on apoptosis-related gene expressions in lungs from rats. Regul Toxicol Pharmacol 43(3):272–279

    Article  CAS  Google Scholar 

  • Bethel RA, Sheppard D, Geffroy B,Tam E, Nadel JA, Boushey HA (1985) Effects of 0.25 ppm sulfur dioxide on airway resistance in freely breathing, heavily exercising, asthmatic subjects. Am Rev Respir Dis 131:659–661

    CAS  Google Scholar 

  • Blumenthal MN (2005) The role of genetics in the development of asthma and atopy. Curr Opin Allergy Clin Immunol 5(2):141–145

    Article  CAS  Google Scholar 

  • Bousquet J, Ansotegui IJ, van Ree R, Burney PG, Zuberbier T, Van Cauwenberge P (2004) European Union meets the challenge of the growing importance of allergy and asthma in Europe. Allergy 59:1–4

    Article  CAS  Google Scholar 

  • Burgel PR, Nadel JA (2004) Role of epidermal growth factor receptor activation in epithelial cell repair and mucin production in airway epithelium. Thorax 59:992–996

    Article  Google Scholar 

  • Cai FF, Yang J, Ni L (2006) The influence of corticosteroid on COX-1 and COX-2 mRNA expression in lung of asthmatic rats. J Pract Med 22(5):504–506

    CAS  Google Scholar 

  • Derya K (2003) The effects of ageing and sulfur dioxide inhalation exposure on visual-evoked potentials, antioxidant enzyme systems, and lipid-peroxidation levels of the brain and eye. Neurotoxicol Teratol 25:587–598

    Article  CAS  Google Scholar 

  • Evans JF, Kargman SL (2004) Cancer and cyclooxygenase-2 (COX-2) inhibition. Curr Pharm Des 10(6):627–634

    Article  CAS  Google Scholar 

  • Goyal SK (2001) Use of rosaniline hydrochloride dye for atmospheric SO2 determination and method sensitivity analysis. J Environ Monit 3:666–670

    Article  CAS  Google Scholar 

  • Grella E, Paciocco G, Caterino U, Mazzarella G (2002) Respiratory function and atmospheric pollution. Monaldi Arch Chest Dis 57(3–4):196–199

    CAS  Google Scholar 

  • Hansson SO, Rud´en C (2006) Evaluating the risk decision process. Toxicology 218:100–111

    Article  CAS  Google Scholar 

  • Harris SG, Padilla J, Koumas L, Ray D, Phipps RP (2002) Prostaglandins as modulators of Immunity. Trends Immunol 23:144–150

    Article  CAS  Google Scholar 

  • Holgate S, Lackie P, Davies DE, Roche RW, Walls AF (1999) The bronchial epithelium as a key regulator of airway inflammation and remodeling in asthma. Clin Exp Allergy 29:90

    Article  Google Scholar 

  • Hylkema MN, Hoekstra MO, Luinge M, Timens W (2002) The strength of the OVA-induced airway inflammation in rats is strain dependent. Clin Exp Immunol 129(3):390–396

    Article  CAS  Google Scholar 

  • Jaworek J, Bonior J, Tomaszewska R, Jachimczak B, Kot M, Bielański W, Pawlik WW, Konturek SJ (2001) Involvement of cycloxygenase-derived prostaglandin E and nitric oxide in the protection of rat pancreas aforded by low dose of hpopolysaccharide. J Physiol Pharmaco1 52:07–126

    Google Scholar 

  • Li R, Meng Z, Xie J (2007) Effects of sulfur dioxide on the expressions of MUC5AC and ICAM-1 in airway of asthmatic rats. Regul Toxicol Pharmacol 48:284–291

    Article  CAS  Google Scholar 

  • Linn WS, Avol EL, Peng R, Shamoo DA, Hackney JD (1987) Replicated dose-response study of sulfur dioxide effects in normal, atopic and asthmatic volunteers. Am Rev Respir Dis 136:1127–1134

    CAS  Google Scholar 

  • Meng Z (2003) Oxidative damage of sulfur dioxide on various organs of mice: sulfur dioxide is a systemic oxidative damage agent. Inhal Toxicol 15:181–195

    Article  CAS  Google Scholar 

  • Meng Z, Qin G, Zhang B (2005) DNA damage in mice treated with sulfur dioxide by inhalation. Environ Mol Mutagen 46(3):150–155

    Article  CAS  Google Scholar 

  • Nadel JA (2001) Role of epidermal growth factor receptor activation in regulating mucin synthesis. Respir Res 2(2):85–89

    Article  CAS  Google Scholar 

  • Nie A, Meng Z (2005) Sulfur dioxide derivative modulation of potassium channels in rat ventricular myocytes. Arch Biochem Biophys 442(2):187–195

    Article  CAS  Google Scholar 

  • Pang L, Knox AJ (1997) Effect of intereukin-1 beta, tumour necrosis factor-alpha and interferon-gamma on the induction of cyclooxygenase-2 in cultured human airway smooth muscle cell. Br J Pharmacol 121:579–587

    Article  CAS  Google Scholar 

  • Park GY, Christman JW (2006) Involvement of cyclooxygenase-2 and prostaglandins in the molecular pathogenesis of inflammatory lung diseases. Am J Physiol Lung Cell Mol Physiol 290:L797–L805

    Article  CAS  Google Scholar 

  • Pavord ID, Tattersfield AE (1995) Bronchoprotective role for endogenous prostaglandin E2. Lancet 345(8947):436–438

    Article  CAS  Google Scholar 

  • Phipps S, Benyahia F, Ou TT, Barkans J, Robinson DS, Kay AB (2004) Acute allergen-induced airway remodeling in atopic asthma. Am J Respir Cell Mol Biol 31:626–632

    Article  CAS  Google Scholar 

  • Pilegaard K, Madsen C (2004) An oral Brown Norway rat model for food allergy: comparison of age, sex, dosing volume, and allergen preparation. Toxicology 196:247–257

    Article  CAS  Google Scholar 

  • Pohunek P, Warner JO, Turzikova J, Kudrmann J, Roche WR (2005) Markers of eosinophilic inflammation and tissue re-modelling in children before clinically diagnosed bronchial asthma. Pediatr Allergy Immunol 16:43–51

    Article  CAS  Google Scholar 

  • Profita M, Sala A, Bonanno A, Riccobono L, Siena L, Melis MR, Di Giorgi R, Mirabella F, Gjomarkaj M, Bonsignore G, Vignola AM (2003) Increased prostaglandin E2 concentrations and cyclooxygenase-2 expression in asthmatic subjects with sputum eosinophilia. J Allergy Clin Immunol 112(4):709–716

    Article  CAS  Google Scholar 

  • Qin G, Meng Z (2005) Effect of sulfur dioxide inhalation on CYP1A1 and CYP1A2 in rat liver and lung. Toxicol Lett 160:34–42

    Article  CAS  Google Scholar 

  • Qin G, Meng Z (2006) The expressions of protooncogenes and CYP1A in lungs of rats exposed to sulfur dioxide and benzo(a)pyrene. Regul Toxicol Pharmacol 45:36–43

    Article  CAS  Google Scholar 

  • Riedel F, Naujukat S, Ruschoff J, Petzoldt S, Rieger CH (1992) Sulfur dioxide-induced enhancement of inhalative allergic sensitization: Inhibition by anti-inflammatory treatment. Int Arch Allergy Immunol 98:386–391

    CAS  Google Scholar 

  • Sheppard D, Wong WS, Uehara CF, Nadel JA, Boushey HA (1980) Lower threshold and greater bronchomotor responsiveness of asthmatic subjects to sulfur dioxide. Am Rev Respir Dis 122:873–878

    CAS  Google Scholar 

  • Takeyama K, Dabbagh K, Lee HM, Agustí C, Lausier JA, Ueki IF, Grattan KM, Nadel JA (1999) Epidermal growth factor system regulates mucin production in airways. Proc Natl Acad Sci USA 96:3081–3086

    Article  CAS  Google Scholar 

  • Tseng RY, Li CK (1990) Low level atmospheric sulfur dioxide pollution and childhood asthma. Ann Allergy 65(5):379–383

    CAS  Google Scholar 

  • Vancheri C, Mastruzzo C, Sortino MA, Crimi N (2004) The lung as a privileged site for the beneficial actions of PGE2. Trends Immunol 25:40–46

    Article  CAS  Google Scholar 

  • Wang W, Li Y (2003) Effect of desamethasone on the expression of collagen and transforming growth factor-(1 in asthmatic rats. Acta Univ Med Nanjing (Nat Sci) 23(6):595–597

    CAS  Google Scholar 

  • Wu Y, Zhou H, Xu Y, Li S (2006) Enhanced expression of urocortin in lung tissues of rats with allergic asthma. Biochem Biophys Res Commun 341(2):532–540

    Article  CAS  Google Scholar 

Download references

Acknowledgment

This research was supported by grant No. 20677035 from the National Natural Science Foundation of China.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Ziqiang Meng.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Li, R., Meng, Z. & Xie, J. Effects of Sulfur Dioxide on the Expressions of EGF, EGFR, and COX-2 in Airway of Asthmatic Rats. Arch Environ Contam Toxicol 54, 748–757 (2008). https://doi.org/10.1007/s00244-007-9054-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00244-007-9054-9

Keywords

Navigation