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Corticosteroids affect nitric oxide generation, total free radicals production, and nitric oxide synthase activity in monocytes of asthmatic patients

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Abstract

Airways inflammation, a pathological hallmark of asthma, is associated with the recruitment of pro-inflammatory and inflammatory cells like eosinophils, polymorphonuclear leucocytes cells, mononuclear cells, macrophages, epithelial desquamation, and airways remodeling with sub-epithelial fibrosis. Activated inflammatory cells along with the resident cells can generate pro-inflammatory mediators including oxidants such as superoxide radicals, reactive oxygen species (ROS), and reactive nitrogen species. One of such inflammatory mediator that has received considerable attention is the nitric oxide (NO•) generated by pulmonary macrophageal/epithelial cells. In this study, we have explored that systemic monocytes also get activated in asthma to produce oxidants like ROS and NO•. We estimated the NO• production, nitric oxide synthase (NOS) activity, inducible NOS (iNOS) mRNA levels and total free radical activity (TFRA) in blood monocytes of healthy control subjects, untreated asthmatic patients, patients on corticosteroid for less than 6 months and patients on corticosteroid for more than 6 months. Increase in NOS activity, NO• levels, and TFRA was observed in monocytes of asthmatic patients. The increase was found to be associated with the transcriptional upregulation of iNOS gene and severity of disease. Highest values of NOS activity, NO•, and iNOS mRNA were found in the patients with acute asthma. Corticosteroid administration was found to be effective in reversing the induction of iNOS mRNA levels, NOS activity and NO• levels. Corticosteroids controlled asthma appears to have association with NOS, NO•, and TFRA in systemic monocytes of the patients.

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Abbreviations

AMs:

Alveolar macrophages

DTT:

Dithiothreitol

FMLP:

N-formyl-methionyl-leucyl phenylemine

eNOS:

Endothelial NOS

FAD:

Flavin adenine dinucleotide

iNOS:

Inducible NOS

LCPS:

Luminescence counts per second

NO:

Nitric oxide

NADPH:

Nucleotide β-Nicotinamide adenine dinucleotide phosphate, reduced

PMA:

Phorbol myristate acetate

PMN:

Polymorphonuclear leucocytes cells

ROS:

Reactive oxygen species

RNS:

Reactive nitrogen species

TFRA:

Total free radical activity

References

  1. Bernstein DI (2008) ABCs of asthma. Clin Cornerstone 8:9–25

    Article  PubMed  Google Scholar 

  2. Fireman P (2003) Understanding asthma pathophysiology. Allergy Asthma Proc 24:79–83

    CAS  PubMed  Google Scholar 

  3. Dunnil MS, Massarella GR, Anderson JA (1969) A quantitative anatomy of the bronchi in normal subjects, in status asthmatics, in chronic bronchitis and in emphysema. Thorax 24:176–179

    Article  Google Scholar 

  4. Raphael GD, Metcalfe CD (1986) Mediators of airway inflammation. Eur J Respir Dis 60:44–56

    Google Scholar 

  5. Andreadis AA, Hazen SL, Comhair SA, Erzurum SC (2003) Oxidative and nitrosative events in asthma. Free Radic Biol Med 35:213–225

    Article  CAS  PubMed  Google Scholar 

  6. Henricks PA, Nijkamp FP (2001) Reactive oxygen species as mediators in asthma. Pulm Pharmacol Ther 14:409–420

    Article  CAS  PubMed  Google Scholar 

  7. Palmer RMJ, Ferridge AG, Moncada S (1987) Nitric oxide release accounts for the biological activity of endothelium derived relaxing factor. Nature 327:524–526

    Article  CAS  PubMed  Google Scholar 

  8. Hamid Q, Springall DR, Riveros-Moreno V, Chanez P, Howarth P, Redington A, Bousquet J, Godard P, Holgate S, Polak JM (1993) Induction of NOS in asthma. Lancet 342:1510–1513

    Article  CAS  PubMed  Google Scholar 

  9. Cluzel M, Damon M, Chanez P, Bousquet J, Crastes de Paulet A, Michel FB, Godard P (1987) Enhanced alveolar cell luminol dependent chemiluminescence in asthma. J Allergy Clin Immunol 80:195–201

    Article  CAS  PubMed  Google Scholar 

  10. Vachier I, Damon H, Le-Doucon C, De paulet Chanez P, Michel FB, Godard P (1992) Increased oxygen species generation in blood monocytes of asthmatic patients. Am Rev Respir Dis 146:1161–1166

    CAS  PubMed  Google Scholar 

  11. Chanez P, Dent G, Yukawa T, Barnes PJ, Chung KF (1990) Generation of oxygen free radicals from blood eosinophiles from asthma patients after stimulation with PAF or Phorbol ester. Eur Respir J 3:1002–1007

    CAS  PubMed  Google Scholar 

  12. Jarjour MN, Calhoun WJ (1994) Enhanced production on oxygen radicals in asthma. J Lab Clin Med 123:131–136

    CAS  PubMed  Google Scholar 

  13. Newton R (2000) Occasional review. Molecular mechanisms of glucocorticoid action: what is important? Thorax 55:603–613

    Article  CAS  PubMed  Google Scholar 

  14. Tanizaki Y, Hosokawa M, Goda Y, Akagi K, Takeyama H, Kimura I (1982) Numerical changes in blood monocytes in bronchial asthma. Acta Med Okayama 36:341–348

    CAS  PubMed  Google Scholar 

  15. Ibeth G, Joanna I, Aldona Dembiska K, Joanna P, Alicja W, Polus A, Iwona G, Stanisław B, Małgorzata M, Andrzej S (1998) Determination of nitrite/nitrate in human biological material by the simple Griess reaction. Clin Chim Acta 274:177–188

    Article  Google Scholar 

  16. Berdt DS, Snyder SH (1990) Isolation of NOS, acalmodulin requiring enzyme. Proc Natl Acad Sci 87:682–685

    Article  Google Scholar 

  17. Chomczynski P, Sacchi N (1987) Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem 162:156–159

    Article  CAS  PubMed  Google Scholar 

  18. Allen RC, Loose LD (1976) Phagocytic activation of luminol dependent chemiluminescence in rabbit alveolar and peritoneal macrophages. Biochem Biophys Res Commun 69:245–252

    Article  CAS  PubMed  Google Scholar 

  19. Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248–254

    Article  CAS  PubMed  Google Scholar 

  20. Yates DH, Kharitnov SA, Robbins RA, Thomas PS, Barnes PJ (1995) Effects of a NOS inhibitor and a glucocorticoid on exhaled NO. Am J Respir Crit Care Med 152:892–896

    CAS  PubMed  Google Scholar 

  21. Bowler RP, Crapo JD (2002) Oxidative stress in allergic respiratory diseases. J Allergy Clin Immunol 110:349–356

    Article  CAS  PubMed  Google Scholar 

  22. Batra J, Singh TP, Mabalirajan U, Sinha A, Prasad R, Ghosh B (2007) Association of inducible nitric oxide synthase with asthma severity, total serum immunoglobulin E and blood eosinophil levels. Thorax 62:16–22

    Article  PubMed  Google Scholar 

  23. Lorsbach RB, Murphy WJ, Lowenstein CJ, Snyder SH (1993) Expression of NOS gene in mouse macrophages activated for tumor cell killing: molecular basis for the synergy between interferon gamma and lipopolysaccharide. J Biol Chem 268:1908–1913

    CAS  PubMed  Google Scholar 

  24. Vodovotz Y, Bogdan C, Paik J, Xie QW, Nathan C (1993) Mechanism of suppression of macrophges. NO release by TGF beta. J Exp Med 178:605–613

    Article  CAS  PubMed  Google Scholar 

  25. Radowski MW, Palmer RMJ, Mocada S (1990) Glucocorticoids inhibit the expression of an inducible but not constitutive NOS in vascular epithelial cell. Proc Natl Acad Sci 87:10043–11049

    Article  Google Scholar 

  26. Puckett JL, George SC (2008) Partitioned exhaled nitric oxide to non-invasively assess asthma. Respir Physiol Neurobiol 163:166–177

    Article  CAS  PubMed  Google Scholar 

  27. Meltzer S, Goldberg B, Lad P, Easton J (1989) Superoxide generation and its modulation by adenosine in the neutrophiles of subjects with asthma. J Allergy Clin Immunol 83:960–966

    Article  CAS  PubMed  Google Scholar 

  28. Sedgwick JB, Kager KM, Busse WW (1990) Superoxide generation by hypodense eosinophils from patients with asthma. Am Rev Respir Dis 142:120–125

    CAS  PubMed  Google Scholar 

  29. Calhoun WJ, Bush RK (1990) Enhanced ROS metabolism of airspace cells and airway inflammation follow antigen challenge in human asthma. J Allergy Clin Immunol 86:306–313

    Article  CAS  PubMed  Google Scholar 

  30. Flower RJ, Rothwill NJ (1994) Lipocortin. Cellular mechanism and clinical relevance. Trends Pharmacol Sci 5:71–76

    Article  Google Scholar 

  31. Bromberg Y, Pich E (1994) Unsaturated fatty acids as second messengers of superoxide generation by macrophages. Trends Pharmacol Sci 15:71–76

    Article  Google Scholar 

  32. Schutz RM, Manda SKW, Altom MG (1995) Effect of various inhibitors of arachidonic acid oxygenation in macrophage superoxide release and tumoricidal activity. J Immunol 135:2040–2044

    Google Scholar 

  33. Majori M, Vachier I, Godard P, Farce M, Bousquet J, Chanez P (1998) Superoxide anion production by monocytes of corticosteroid-treated asthmatic patients. Eur Respir J 11:133–138

    Article  CAS  PubMed  Google Scholar 

  34. Rana JS, Mittleman MA, Sheikh J, Hu FB, Manson JE, Colditz GA, Speizer FE, Barr RG, Camargo CA (2004) Chronic obstructive pulmonary disease, asthma, and risk of type 2 diabetes in women. Diabetes Care 27:2478–2484

    Article  PubMed  Google Scholar 

  35. Faul JL, Wilson SR, Chu JW, Canfield J, Kuschner WG (2009) The effect of an inhaled corticosteroid on glucose control in type 2 diabetes. Clin Med Res 7:14–20

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

Postgraduate Institute of Medical Education and Research is fully acknowledged.

Conflict of interest

The authors declare no conflicts of interest.

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Authors and Affiliations

  1. Department of Biophysics, Postgraduate Institute of Medical Education and Research, Chandigarh, India

    Krishan Lal Khanduja, Gaurav Kaushik, Suchit Khanduja & Chander Mohan Pathak

  2. Department of Pulmonary Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh, India

    Judy Laldinpuii & Degambar Behera

Authors
  1. Krishan Lal Khanduja
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  2. Gaurav Kaushik
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  3. Suchit Khanduja
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  4. Chander Mohan Pathak
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Correspondence to Krishan Lal Khanduja.

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Khanduja, K.L., Kaushik, G., Khanduja, S. et al. Corticosteroids affect nitric oxide generation, total free radicals production, and nitric oxide synthase activity in monocytes of asthmatic patients. Mol Cell Biochem 346, 31–37 (2011). https://doi.org/10.1007/s11010-010-0588-1

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