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 Citations (Scopus)

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

Fingerprint

Diaphragm
Research Ethics Committees
Nitric Oxide
Respiration
NG-Nitroarginine Methyl Ester
Cytokines
Up-Regulation
NF-kappa B
Interleukin-6
Nitric Oxide Donors
Down-Regulation
Nitroarginine
p38 Mitogen-Activated Protein Kinases
Interleukin-1
Nitric Oxide Synthase
Interleukin-10
Chronic Obstructive Pulmonary Disease
Interleukin-2
Wistar Rats
Asthma

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

Cite this

Sigala, I., Zacharatos, P., Boulia, S., Toumpanakis, D., Michailidou, T., Parthenis, D., ... 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

Nitric oxide regulates cytokine induction in the diaphragm in response to inspiratory resistive breathing. / Sigala, Ioanna; Zacharatos, Panayiotis; Boulia, Stavroula; Toumpanakis, Dimitris; Michailidou, Tatiana; Parthenis, Dimitris; Roussos, Charis; Papapetropoulos, Andreas; Hussain, Sabah N.; Vassilakopoulos, Theodoros.

In: Journal of Applied Physiology, Vol. 113, No. 10, 15.11.2012, p. 1594-1603.

Research output: Contribution to journalArticle

Sigala, I, Zacharatos, P, Boulia, S, Toumpanakis, D, Michailidou, T, Parthenis, D, Roussos, C, Papapetropoulos, A, Hussain, SN & Vassilakopoulos, T 2012, 'Nitric oxide regulates cytokine induction in the diaphragm in response to inspiratory resistive breathing', Journal of Applied Physiology, vol. 113, no. 10, pp. 1594-1603. https://doi.org/10.1152/japplphysiol.00233.2012
Sigala, Ioanna ; Zacharatos, Panayiotis ; Boulia, Stavroula ; Toumpanakis, Dimitris ; Michailidou, Tatiana ; Parthenis, Dimitris ; Roussos, Charis ; Papapetropoulos, Andreas ; Hussain, Sabah N. ; Vassilakopoulos, Theodoros. / Nitric oxide regulates cytokine induction in the diaphragm in response to inspiratory resistive breathing. In: Journal of Applied Physiology. 2012 ; Vol. 113, No. 10. pp. 1594-1603.
@article{328f6a3282c04cfe84f0ba3292b2d2b2,
title = "Nitric oxide regulates cytokine induction in the diaphragm in response to inspiratory resistive breathing",
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.",
author = "Ioanna Sigala and Panayiotis Zacharatos and Stavroula Boulia and Dimitris Toumpanakis and Tatiana Michailidou and Dimitris Parthenis and Charis Roussos and Andreas Papapetropoulos and Hussain, {Sabah N.} and Theodoros Vassilakopoulos",
year = "2012",
month = "11",
day = "15",
doi = "10.1152/japplphysiol.00233.2012",
language = "English (US)",
volume = "113",
pages = "1594--1603",
journal = "Journal of Applied Physiology",
issn = "8750-7587",
publisher = "American Physiological Society",
number = "10",

}

TY - JOUR

T1 - Nitric oxide regulates cytokine induction in the diaphragm in response to inspiratory resistive breathing

AU - Sigala, Ioanna

AU - Zacharatos, Panayiotis

AU - Boulia, Stavroula

AU - Toumpanakis, Dimitris

AU - Michailidou, Tatiana

AU - Parthenis, Dimitris

AU - Roussos, Charis

AU - Papapetropoulos, Andreas

AU - Hussain, Sabah N.

AU - Vassilakopoulos, Theodoros

PY - 2012/11/15

Y1 - 2012/11/15

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84869201635&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84869201635&partnerID=8YFLogxK

U2 - 10.1152/japplphysiol.00233.2012

DO - 10.1152/japplphysiol.00233.2012

M3 - Article

C2 - 22961265

AN - SCOPUS:84869201635

VL - 113

SP - 1594

EP - 1603

JO - Journal of Applied Physiology

JF - Journal of Applied Physiology

SN - 8750-7587

IS - 10

ER -