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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

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Acknowledgments

Postgraduate Institute of Medical Education and Research is fully acknowledged.

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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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