Nitric oxide regulates cytokine induction in the diaphragm in response to inspiratory resistive breathing

Ioanna Sigala, Panayiotis Zacharatos, Stavroula Boulia, Dimitris Toumpanakis, Tatiana Michailidou, Dimitris Parthenis, Charis Roussos, Andreas Papapetropoulos, Sabah N. Hussain, Theodoros Vassilakopoulos

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

Nitric oxide regulates cytokine induction in the diaphragm in response to inspiratory resistive breathing. J Appl Physiol 113: 1594-1603, 2012. First published September 6, 2012; doi:10.1152/japplphysiol.00233.2012.-Resistive breathing (encountered in chronic obstructive pulmonary disease and asthma) results in cytokine upregulation and decreased nitric oxide (NO) levels in the strenuously contracting diaphragm. NO can regulate gene expression. We hypothesized that endogenously produced NO downregulates cytokine production triggered by strenuous diaphragmatic contraction. Wistar rats treated with vehicle, the nonselective NO synthase inhibitor NG-nitro-L-arginine-methylester (L-NAME), or the NO donor diethylenetriamine-NONOate (DETA) were subjected to inspiratory resistive breathing (IRB; 50% of maximal inspiratory pressure) for 6 h or sham operation. Additional groups of rats were subjected to IRB for 6 h with concurrent administration of L-NAME and inhibitors of NF-kB (BAY-11-7082), ERK1/2 (PD98059), or P38 (SB203580). Inhibition of NO production (with L-NAME) resulted in upregulation of IRB-induced diaphragmatic IL-6, IL-10, IL-2, TNF-α, and IL-1β levels by 50%, 53%, 60%, 47%, and 45%, respectively. In contrast, the NO donor (DETA) attenuated the IRB-induced cytokine upregulation to levels characteristic of quietly breathing animals. L-NAME augmented IRB-induced activation of MAPKs (P38 and ERK1/2) and NF-kB, whereas DETA triggered the opposite effect. NF-B and ERK1/2 inhibition in L-NAME-treated animals blunted the L-NAMEinduced cytokine upregulation except IL-6, whereas P38 inhibition blunted all (including IL-6) cytokine upregulation. NO downregulates IRB-induced cytokine production in the strenuously contracting diaphragm through its action on MAPKs and NF-kB.

Original languageEnglish (US)
Pages (from-to)1594-1603
Number of pages10
JournalJournal of Applied Physiology
Volume113
Issue number10
DOIs
StatePublished - Nov 15 2012
Externally publishedYes

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

Fingerprint Dive into the research topics of 'Nitric oxide regulates cytokine induction in the diaphragm in response to inspiratory resistive breathing'. Together they form a unique fingerprint.

  • Cite this

    Sigala, I., Zacharatos, P., Boulia, S., Toumpanakis, D., Michailidou, T., Parthenis, D., Roussos, C., Papapetropoulos, A., Hussain, S. N., & Vassilakopoulos, T. (2012). Nitric oxide regulates cytokine induction in the diaphragm in response to inspiratory resistive breathing. Journal of Applied Physiology, 113(10), 1594-1603. https://doi.org/10.1152/japplphysiol.00233.2012