Skip to main content
Top
Published in: Respiratory Research 1/2005

Open Access 01-12-2005 | Research

Immune sensitization of equine bronchus: glutathione, IL-1β expression and tissue responsiveness

Authors: MG Matera, L Calzetta, A Peli, A Scagliarini, C Matera, M Cazzola

Published in: Respiratory Research | Issue 1/2005

Login to get access

Abstract

Background

Increasing clinical epidemiological and experimental evidence indicates that excess of production of reactive oxygen free radicals (ROS) induced by an oxidative stress is involved in the pathogenesis of a number of human airway disorders, as well as equine recurrent airway obstruction. Free-radicals modulate the activation of transcription factors, such as nuclear factor-(NF)-κB and activator protein (AP)-1, in several different cells. This activation leads to expression of many pro-inflammatory cytokines, including interleukin (IL)-1β. We have hypothesized that equine airway sensitization might induce an oxidative stress and increase the ROS production, which in turn might enhance a production of IL-1β and airway hyperresponsiveness.

Methods

We have examined the effect of passive sensitization on IL-1β mRNA expression and electrical field stimulation (EFS)-induced contraction in equine isolated bronchi, and the potential interference of reduced-glutathione (GSH), an antioxidant, with these responses. Bronchi passively sensitized with serum from animals suffering from heaves and having high total level of IgE, and control tissues, either pretreated or not with GSH (100 μM), were used to quantify IL-1β mRNA. Other tissues were used to study the effect of EFS (3–10–25 Hz).

Results

Mean IL-1β mRNA expression was higher in passively sensitized than in control rings. GSH significantly (p < 0.05) reduced the IL-1β mRNA expression only in passively sensitized bronchi. ELF induced a frequency-dependent contraction in both non-sensitized and passively sensitized tissues, with a significantly greater response always observed in sensitized tissues. GSH did not modify the EFS-induced contraction in non-sensitized bronchi, but significantly (p < 0.05) decreased it in passively sensitized tissues.

Conclusion

Our data indicate that the passive sensitization of equine bronchi induces inflammation and hyperresponsiveness. These effects might be due to an oxidative stress because a pretreatment with GSH decreased the increased IL-1β mRNA expression and responsiveness to EFS of passively sensitized bronchi.
Literature
1.
go back to reference MacNee W: Oxidative stress and lung inflammation in airways disease. Eur J Pharmacol 2001, 429:195–207.CrossRefPubMed MacNee W: Oxidative stress and lung inflammation in airways disease. Eur J Pharmacol 2001, 429:195–207.CrossRefPubMed
2.
go back to reference Henricks PAJ, Nijkamp FP: Reactive oxygen species as mediators in asthma. Pulm Pharmacol Ther 2001, 14:409–421.CrossRefPubMed Henricks PAJ, Nijkamp FP: Reactive oxygen species as mediators in asthma. Pulm Pharmacol Ther 2001, 14:409–421.CrossRefPubMed
3.
go back to reference Langen RC, Korn SH, Wouters EF: ROS in the local and systemic pathogenesis of COPD. Free Radic Biol Med 2003, 35:226–235.CrossRefPubMed Langen RC, Korn SH, Wouters EF: ROS in the local and systemic pathogenesis of COPD. Free Radic Biol Med 2003, 35:226–235.CrossRefPubMed
4.
go back to reference Art T, Kirschvink N, Smith N, Lekeux P: Indices of oxidative stress in blood and pulmonary epithelium lining fluid in horses suffering from recurrent airway obstruction. Equine Vet J 1999, 31:397–401.CrossRefPubMed Art T, Kirschvink N, Smith N, Lekeux P: Indices of oxidative stress in blood and pulmonary epithelium lining fluid in horses suffering from recurrent airway obstruction. Equine Vet J 1999, 31:397–401.CrossRefPubMed
5.
go back to reference Deaton CM, Marlin DJ, Smith NC, Roberts CA, Harris PA, Schroter RC, Kelly FJ: Antioxidant and inflammatory responses of healthy horses and horses affected by recurrent airway obstruction to inhaled ozone. Equine Vet J 2005, 37:243–249.CrossRefPubMed Deaton CM, Marlin DJ, Smith NC, Roberts CA, Harris PA, Schroter RC, Kelly FJ: Antioxidant and inflammatory responses of healthy horses and horses affected by recurrent airway obstruction to inhaled ozone. Equine Vet J 2005, 37:243–249.CrossRefPubMed
6.
go back to reference Blesa S, Cortijo J, Mata M, Serrano A, Closa D, Santangelo F, Estrela JM, Suchankova J, Morcillo EJ: Oral N-acetylcysteine attenuates the rat pulmonary inflammatory response to antigen. Eur Respir J 2003, 21:394–400.CrossRefPubMed Blesa S, Cortijo J, Mata M, Serrano A, Closa D, Santangelo F, Estrela JM, Suchankova J, Morcillo EJ: Oral N-acetylcysteine attenuates the rat pulmonary inflammatory response to antigen. Eur Respir J 2003, 21:394–400.CrossRefPubMed
7.
go back to reference Kirschvink N, Fievez L, Bougnet V, Art T, Degand G, Smith N, Marlin D, Roberts C, Harris P, Lekeux P: Effect of nutritional antioxidant supplementation on systemic and pulmonary antioxidants status, airway inflammation and lung function in heaves-affected horses. Equine Vet J 2002, 34:705–712.CrossRefPubMed Kirschvink N, Fievez L, Bougnet V, Art T, Degand G, Smith N, Marlin D, Roberts C, Harris P, Lekeux P: Effect of nutritional antioxidant supplementation on systemic and pulmonary antioxidants status, airway inflammation and lung function in heaves-affected horses. Equine Vet J 2002, 34:705–712.CrossRefPubMed
8.
go back to reference Kirschvink N, Art T, Smith N, Lekeux P: Effects of exercise and COPD crisis on isoprostane concentration in plasma and bronchoalveolar lavage fluid in horses. Equine Vet J Suppl 2001, 30:88–91. Kirschvink N, Art T, Smith N, Lekeux P: Effects of exercise and COPD crisis on isoprostane concentration in plasma and bronchoalveolar lavage fluid in horses. Equine Vet J Suppl 2001, 30:88–91.
9.
go back to reference Kirschvink N, Art T, Smith N, Lekeux P: Bronchoconstrictive properties of inhaled 8-epi-PGF 2α in healthy and heaves-susceptible horses. Vet Res 2001, 32:397–407.CrossRefPubMed Kirschvink N, Art T, Smith N, Lekeux P: Bronchoconstrictive properties of inhaled 8-epi-PGF in healthy and heaves-susceptible horses. Vet Res 2001, 32:397–407.CrossRefPubMed
10.
go back to reference Sanders SP, Zweier JL, Harrison SJ, Trush MA, Rembish SJ, Liu MC: Spontaneous oxygen radical production at sites of antigen challenge in allergic subjects. Am J Respir Crit Care Med 1995, 151:1725–1733.CrossRefPubMed Sanders SP, Zweier JL, Harrison SJ, Trush MA, Rembish SJ, Liu MC: Spontaneous oxygen radical production at sites of antigen challenge in allergic subjects. Am J Respir Crit Care Med 1995, 151:1725–1733.CrossRefPubMed
11.
go back to reference Morcillo EJ, Estrela J, Cortijo J: Oxidative stress and pulmonary inflammation: pharmacological intervention with antioxidants. Pharmacol Res 1999, 40:393–404.CrossRefPubMed Morcillo EJ, Estrela J, Cortijo J: Oxidative stress and pulmonary inflammation: pharmacological intervention with antioxidants. Pharmacol Res 1999, 40:393–404.CrossRefPubMed
12.
go back to reference Bureau F, Delhalle S, Bonizzi G, Fievez L, Dogne S, Kirschvink N, Vanderplasschen A, Merville MP, Bours V, Lekeux P: Mechanisms of persistent NF-κB activity in the bronchi of an animal model of asthma. J Immunol 2000, 165:5822–5830.CrossRefPubMed Bureau F, Delhalle S, Bonizzi G, Fievez L, Dogne S, Kirschvink N, Vanderplasschen A, Merville MP, Bours V, Lekeux P: Mechanisms of persistent NF-κB activity in the bronchi of an animal model of asthma. J Immunol 2000, 165:5822–5830.CrossRefPubMed
13.
go back to reference Hakonarson H, Herrick DJ, Serrano PG, Grunstein MM: Autocrine role of interleukin 1β in altered responsiveness of atopic asthmatic sensitized airway smooth muscle. J Clin Invest 1997, 99:117–124.CrossRefPubMedPubMedCentral Hakonarson H, Herrick DJ, Serrano PG, Grunstein MM: Autocrine role of interleukin 1β in altered responsiveness of atopic asthmatic sensitized airway smooth muscle. J Clin Invest 1997, 99:117–124.CrossRefPubMedPubMedCentral
14.
go back to reference Baeuerle PA, Baichwal VR: NF-κB as a frequent target for immunosuppressive and anti-inflammatory molecules. Adv Immunol 1997, 65:111–137.CrossRefPubMed Baeuerle PA, Baichwal VR: NF-κB as a frequent target for immunosuppressive and anti-inflammatory molecules. Adv Immunol 1997, 65:111–137.CrossRefPubMed
15.
go back to reference Bureau F, Bonizzi G, Kirschvink N, Delhalle S, Desmecht D, Merville MP, Bours V, Lekeux P: Correlation between nuclear factor-κB activity in bronchial brushing samples and lung dysfunction in an animal model of asthma. Am J Respir Crit Care Med 2000, 161:1314–1321.CrossRefPubMed Bureau F, Bonizzi G, Kirschvink N, Delhalle S, Desmecht D, Merville MP, Bours V, Lekeux P: Correlation between nuclear factor-κB activity in bronchial brushing samples and lung dysfunction in an animal model of asthma. Am J Respir Crit Care Med 2000, 161:1314–1321.CrossRefPubMed
16.
go back to reference Giguere S, Viel L, Lee E, MacKay RJ, Hernandez J, Franchini M: Cytokine induction in pulmonary airways of horses with heaves and effect of therapy of inhaled fluticasone propionate. Vet Immunol Immunopathol 2002, 85:147–158.CrossRefPubMed Giguere S, Viel L, Lee E, MacKay RJ, Hernandez J, Franchini M: Cytokine induction in pulmonary airways of horses with heaves and effect of therapy of inhaled fluticasone propionate. Vet Immunol Immunopathol 2002, 85:147–158.CrossRefPubMed
17.
go back to reference Watson N, Bodtke K, Coleman RA, Dent G, Morton BE, Ruhlmann E, Magnussen H, Rabe KF: Role of IgE in hyperresponsiveness induced by passive sensitization of human airways. Am J Respir Crit Care Med 1997, 155:839–844.CrossRefPubMed Watson N, Bodtke K, Coleman RA, Dent G, Morton BE, Ruhlmann E, Magnussen H, Rabe KF: Role of IgE in hyperresponsiveness induced by passive sensitization of human airways. Am J Respir Crit Care Med 1997, 155:839–844.CrossRefPubMed
18.
go back to reference Rabe KF: Mechanisms of immune sensitization of human bronchus. Am J Respir Crit Care Med 1998, 158:S167-S170.CrossRef Rabe KF: Mechanisms of immune sensitization of human bronchus. Am J Respir Crit Care Med 1998, 158:S167-S170.CrossRef
19.
go back to reference Schmidt DT, Watson N, Dent G, Ruhlmann E, Branscheid D, Magnussen H, Rabe KF: The effect of selective and non-selective phosphodiesterase inhibitors on allergen- and leukotriene C 4 -induced contractions in passively sensitized human airways. Br J Pharmacol 2000, 131:1607–1618.CrossRefPubMedPubMedCentral Schmidt DT, Watson N, Dent G, Ruhlmann E, Branscheid D, Magnussen H, Rabe KF: The effect of selective and non-selective phosphodiesterase inhibitors on allergen- and leukotriene C 4 -induced contractions in passively sensitized human airways. Br J Pharmacol 2000, 131:1607–1618.CrossRefPubMedPubMedCentral
20.
go back to reference Tizard IR: Veterinary immunology: an Introduction. 7th edition. Philadelphia: Saunders; 2004:145–154. Tizard IR: Veterinary immunology: an Introduction. 7th edition. Philadelphia: Saunders; 2004:145–154.
21.
go back to reference Roberts JA, Thomson NC: The effect of passive sensitization of human bronchial smooth muscle on in vitro sensitivity to histamine. Pulm Pharmacol 1989, 2:103–105.CrossRefPubMed Roberts JA, Thomson NC: The effect of passive sensitization of human bronchial smooth muscle on in vitro sensitivity to histamine. Pulm Pharmacol 1989, 2:103–105.CrossRefPubMed
22.
go back to reference Folkerts G, Klock J, Muijsers RB, Nijkamp FP: Reactive nitrogen and oxygen species in airway inflammation. Eur J Pharmacol 2001, 429:521–562.CrossRef Folkerts G, Klock J, Muijsers RB, Nijkamp FP: Reactive nitrogen and oxygen species in airway inflammation. Eur J Pharmacol 2001, 429:521–562.CrossRef
23.
go back to reference Vachier I, Chanez P, Le Doucen C, Damon M, Descomps B, Godard P: Enhancement of reactive reactive oxygen species formation in stable and unstable asthmatic patients. Eur Resp J 1994, 3:1518–1592. Vachier I, Chanez P, Le Doucen C, Damon M, Descomps B, Godard P: Enhancement of reactive reactive oxygen species formation in stable and unstable asthmatic patients. Eur Resp J 1994, 3:1518–1592.
24.
go back to reference Vachier I, Damon M, Le Doucen C, de Paulet AC, Chanez P, Michel FB, Godard P: Increased oxygen species generation in blood monocytes of asthmatic patients. Am Rev Respir Dis 1992, 146:1161–1166.CrossRefPubMed Vachier I, Damon M, Le Doucen C, de Paulet AC, Chanez P, Michel FB, Godard P: Increased oxygen species generation in blood monocytes of asthmatic patients. Am Rev Respir Dis 1992, 146:1161–1166.CrossRefPubMed
25.
go back to reference Lavoie JP, Maghni K, Desnoyers M, Taha R, Martin JG, Hamid QA: Neutrophilic airway inflammation in horses with heaves is characterized by a Th2-type cytokine profile. Am J Respir Crit Care Med 2001, 164:1410–1413.CrossRefPubMed Lavoie JP, Maghni K, Desnoyers M, Taha R, Martin JG, Hamid QA: Neutrophilic airway inflammation in horses with heaves is characterized by a Th2-type cytokine profile. Am J Respir Crit Care Med 2001, 164:1410–1413.CrossRefPubMed
26.
go back to reference Rahman I, MacNee W: Regulation of redox glutathione levels and gene transcription in lung inflammation: therapeutic approaches. Free Radic Biol Med 2000, 28:1405–1420.CrossRefPubMed Rahman I, MacNee W: Regulation of redox glutathione levels and gene transcription in lung inflammation: therapeutic approaches. Free Radic Biol Med 2000, 28:1405–1420.CrossRefPubMed
27.
go back to reference Rahman I: Oxidative stress and gene transcription in asthma and chronic obstructive pulmonary disease: antioxidant therapeutic targets. Curr Drug Targets Inflamm Allergy 2002, 1:291–315.CrossRefPubMed Rahman I: Oxidative stress and gene transcription in asthma and chronic obstructive pulmonary disease: antioxidant therapeutic targets. Curr Drug Targets Inflamm Allergy 2002, 1:291–315.CrossRefPubMed
28.
go back to reference Ichinose M, Miura M, Tomaki M, Oyake T, Kageyama N, Ikarashi Y, Maruyama Y, Shirato K: Incubation with IgE increases cholinergic neurotransmission in human airways in vitro . Am J Respir Crit Care Med 1996, 154:1272–1276.CrossRefPubMed Ichinose M, Miura M, Tomaki M, Oyake T, Kageyama N, Ikarashi Y, Maruyama Y, Shirato K: Incubation with IgE increases cholinergic neurotransmission in human airways in vitro . Am J Respir Crit Care Med 1996, 154:1272–1276.CrossRefPubMed
29.
go back to reference Ohrui T, Sekizawa K, Yamauchi K, Ohkawara Y, Nakazawa H, Aikawa T, Sasaki H, Takishima T: Chemical oxidant potentiates electrically and acetylcholine-induced contraction in rat trachea: possible involvement of cholinesterase inhibition. J Pharmacol Exp Ther 1991, 259:371–376.PubMed Ohrui T, Sekizawa K, Yamauchi K, Ohkawara Y, Nakazawa H, Aikawa T, Sasaki H, Takishima T: Chemical oxidant potentiates electrically and acetylcholine-induced contraction in rat trachea: possible involvement of cholinesterase inhibition. J Pharmacol Exp Ther 1991, 259:371–376.PubMed
30.
go back to reference Sadeghi-Hashjin G, Folkerts G, Henricks PA, Verheyen AK, van der Linde HJ, van Ark I, Coene A, Nijkamp FP: Peroxynitrite induces airway hyperresponsiveness in guinea pigs in vitro and in vivo . Am J Respir Crit Care Med 1996, 153:1697–1701.CrossRefPubMed Sadeghi-Hashjin G, Folkerts G, Henricks PA, Verheyen AK, van der Linde HJ, van Ark I, Coene A, Nijkamp FP: Peroxynitrite induces airway hyperresponsiveness in guinea pigs in vitro and in vivo . Am J Respir Crit Care Med 1996, 153:1697–1701.CrossRefPubMed
31.
go back to reference Murlas CG, Murphy TP, Lang Z: HOCl causes airway substance P hyperresponsiveness and neutral hypoactivity. Am J Physiol 1990, 258:L361-L368.PubMed Murlas CG, Murphy TP, Lang Z: HOCl causes airway substance P hyperresponsiveness and neutral hypoactivity. Am J Physiol 1990, 258:L361-L368.PubMed
32.
go back to reference Cortijo J, Marti-Cabrera M, de la Asuncion JG, Pallardo FV, Esteras A, Bruseghini L, Vina J, Morcillo EJ: Contraction of human airways by oxidative stress protection by N-acetylcysteine. Free Radic Biol Med 1999, 27:392–400.CrossRefPubMed Cortijo J, Marti-Cabrera M, de la Asuncion JG, Pallardo FV, Esteras A, Bruseghini L, Vina J, Morcillo EJ: Contraction of human airways by oxidative stress protection by N-acetylcysteine. Free Radic Biol Med 1999, 27:392–400.CrossRefPubMed
33.
go back to reference Olszewski MA, Robinson NE, Yu MF, Derksen FJ: Effects of peroxide on isolated trachealis muscle of horses. Am J Vet Res 1995, 56:1479–1485.PubMed Olszewski MA, Robinson NE, Yu MF, Derksen FJ: Effects of peroxide on isolated trachealis muscle of horses. Am J Vet Res 1995, 56:1479–1485.PubMed
34.
go back to reference Blackwell TS, Blackwell TR, Holden EP, Christman BW, Christman JW: In vivo antioxidant treatment suppresses nuclear factor κB activation and neutrophilic lung inflammation. J Immunol 1996, 157:1630–1637.PubMed Blackwell TS, Blackwell TR, Holden EP, Christman BW, Christman JW: In vivo antioxidant treatment suppresses nuclear factor κB activation and neutrophilic lung inflammation. J Immunol 1996, 157:1630–1637.PubMed
35.
go back to reference Barchasz E, Naline E, Molimard M, Moreau J, Georges O, Emonds-Alt X, Advenier C: Interleukin-1β-induced hyperresponsiveness to [Sar 9 ,Met(O 2 ) 11 ]substance P in isolated human bronchi. Eur J Pharmacol 1999, 379:87–95.CrossRefPubMed Barchasz E, Naline E, Molimard M, Moreau J, Georges O, Emonds-Alt X, Advenier C: Interleukin-1β-induced hyperresponsiveness to [Sar 9 ,Met(O 2 ) 11 ]substance P in isolated human bronchi. Eur J Pharmacol 1999, 379:87–95.CrossRefPubMed
36.
go back to reference Tsukagoshi H, Sakamoto T, Xu W, Barnes PJ, Chung KF: Effect of interleukin-1β on airway hyperresponsiveness and inflammation in sensitized and nonsensitized Brown-Norway rats. J Allergy Clin Immunol 1994, 93:464–469.CrossRefPubMed Tsukagoshi H, Sakamoto T, Xu W, Barnes PJ, Chung KF: Effect of interleukin-1β on airway hyperresponsiveness and inflammation in sensitized and nonsensitized Brown-Norway rats. J Allergy Clin Immunol 1994, 93:464–469.CrossRefPubMed
Metadata
Title
Immune sensitization of equine bronchus: glutathione, IL-1β expression and tissue responsiveness
Authors
MG Matera
L Calzetta
A Peli
A Scagliarini
C Matera
M Cazzola
Publication date
01-12-2005
Publisher
BioMed Central
Published in
Respiratory Research / Issue 1/2005
Electronic ISSN: 1465-993X
DOI
https://doi.org/10.1186/1465-9921-6-104

Other articles of this Issue 1/2005

Respiratory Research 1/2005 Go to the issue