Synergistic cytokine-induced nitric oxide production in human alveolar epithelial cells

Soonjo Kwon, Steven George

Research output: Contribution to journalArticle

67 Citations (Scopus)

Abstract

Nitric oxide (NO) is an important mediator molecule in regulating normal airway function, as well as in the pathophysiology of inflammatory airway diseases. In addition, cytokines are potent messenger molecules at sites of inflammation. The specific relationship among IL-1β, TNF-α, and IFN-γ on iNOS induction and NO synthesis in human alveolar epithelial cells has not been determined. In addition, rigorous methods to determine potential synergistic action between the cytokines have not been employed. We exposed monolayer cultures of A549 cells to a factorial combination of three cytokines (IL-1β, TNF-α, and IFN-γ) and three concentrations (0, 5, and 100 ng/mL). TNF-α alone does not induce NO production directly; however, it does have a stimulatory effect on IL-1β-induced NO production. IL-1β and INF-γ both induce NO production alone, yet at different concentration thresholds, and act synergistically when present together. In the presence of all three cytokines, the net effect of NO production exceeds the predicted additive effect of each individual cytokine and the two-way interactions. Several plausible mechanisms of synergy among IL-1β, TNF-α, and IFN-γ in NO production from human alveolar epithelial cells (A549) are proposed. In order to verify the proposed mechanisms of synergy, future experimental and theoretical studies must address several molecular steps through which the iNOS gene is expressed and regulated, as well as the expression and regulation of enzyme cofactors and substrates.

Original languageEnglish (US)
Pages (from-to)348-357
Number of pages10
JournalNitric Oxide - Biology and Chemistry
Volume3
Issue number4
DOIs
StatePublished - Jan 1 1999

Fingerprint

Alveolar Epithelial Cells
Nitric Oxide
Interleukin-1
Cytokines
Molecules
Coenzymes
Epithelial Cells
Action Potentials
Monolayers
Theoretical Models
Genes
Inflammation
Substrates

Keywords

  • A549
  • Interleukin-1β interferon-γ
  • Synergy
  • Tumor necrosis factor-α

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Clinical Biochemistry
  • Cancer Research

Cite this

Synergistic cytokine-induced nitric oxide production in human alveolar epithelial cells. / Kwon, Soonjo; George, Steven.

In: Nitric Oxide - Biology and Chemistry, Vol. 3, No. 4, 01.01.1999, p. 348-357.

Research output: Contribution to journalArticle

@article{85e5bec33b01473aafd04b10dd6d9be5,
title = "Synergistic cytokine-induced nitric oxide production in human alveolar epithelial cells",
abstract = "Nitric oxide (NO) is an important mediator molecule in regulating normal airway function, as well as in the pathophysiology of inflammatory airway diseases. In addition, cytokines are potent messenger molecules at sites of inflammation. The specific relationship among IL-1β, TNF-α, and IFN-γ on iNOS induction and NO synthesis in human alveolar epithelial cells has not been determined. In addition, rigorous methods to determine potential synergistic action between the cytokines have not been employed. We exposed monolayer cultures of A549 cells to a factorial combination of three cytokines (IL-1β, TNF-α, and IFN-γ) and three concentrations (0, 5, and 100 ng/mL). TNF-α alone does not induce NO production directly; however, it does have a stimulatory effect on IL-1β-induced NO production. IL-1β and INF-γ both induce NO production alone, yet at different concentration thresholds, and act synergistically when present together. In the presence of all three cytokines, the net effect of NO production exceeds the predicted additive effect of each individual cytokine and the two-way interactions. Several plausible mechanisms of synergy among IL-1β, TNF-α, and IFN-γ in NO production from human alveolar epithelial cells (A549) are proposed. In order to verify the proposed mechanisms of synergy, future experimental and theoretical studies must address several molecular steps through which the iNOS gene is expressed and regulated, as well as the expression and regulation of enzyme cofactors and substrates.",
keywords = "A549, Interleukin-1β interferon-γ, Synergy, Tumor necrosis factor-α",
author = "Soonjo Kwon and Steven George",
year = "1999",
month = "1",
day = "1",
doi = "10.1006/niox.1999.0242",
language = "English (US)",
volume = "3",
pages = "348--357",
journal = "Nitric Oxide - Biology and Chemistry",
issn = "1089-8603",
publisher = "Academic Press Inc.",
number = "4",

}

TY - JOUR

T1 - Synergistic cytokine-induced nitric oxide production in human alveolar epithelial cells

AU - Kwon, Soonjo

AU - George, Steven

PY - 1999/1/1

Y1 - 1999/1/1

N2 - Nitric oxide (NO) is an important mediator molecule in regulating normal airway function, as well as in the pathophysiology of inflammatory airway diseases. In addition, cytokines are potent messenger molecules at sites of inflammation. The specific relationship among IL-1β, TNF-α, and IFN-γ on iNOS induction and NO synthesis in human alveolar epithelial cells has not been determined. In addition, rigorous methods to determine potential synergistic action between the cytokines have not been employed. We exposed monolayer cultures of A549 cells to a factorial combination of three cytokines (IL-1β, TNF-α, and IFN-γ) and three concentrations (0, 5, and 100 ng/mL). TNF-α alone does not induce NO production directly; however, it does have a stimulatory effect on IL-1β-induced NO production. IL-1β and INF-γ both induce NO production alone, yet at different concentration thresholds, and act synergistically when present together. In the presence of all three cytokines, the net effect of NO production exceeds the predicted additive effect of each individual cytokine and the two-way interactions. Several plausible mechanisms of synergy among IL-1β, TNF-α, and IFN-γ in NO production from human alveolar epithelial cells (A549) are proposed. In order to verify the proposed mechanisms of synergy, future experimental and theoretical studies must address several molecular steps through which the iNOS gene is expressed and regulated, as well as the expression and regulation of enzyme cofactors and substrates.

AB - Nitric oxide (NO) is an important mediator molecule in regulating normal airway function, as well as in the pathophysiology of inflammatory airway diseases. In addition, cytokines are potent messenger molecules at sites of inflammation. The specific relationship among IL-1β, TNF-α, and IFN-γ on iNOS induction and NO synthesis in human alveolar epithelial cells has not been determined. In addition, rigorous methods to determine potential synergistic action between the cytokines have not been employed. We exposed monolayer cultures of A549 cells to a factorial combination of three cytokines (IL-1β, TNF-α, and IFN-γ) and three concentrations (0, 5, and 100 ng/mL). TNF-α alone does not induce NO production directly; however, it does have a stimulatory effect on IL-1β-induced NO production. IL-1β and INF-γ both induce NO production alone, yet at different concentration thresholds, and act synergistically when present together. In the presence of all three cytokines, the net effect of NO production exceeds the predicted additive effect of each individual cytokine and the two-way interactions. Several plausible mechanisms of synergy among IL-1β, TNF-α, and IFN-γ in NO production from human alveolar epithelial cells (A549) are proposed. In order to verify the proposed mechanisms of synergy, future experimental and theoretical studies must address several molecular steps through which the iNOS gene is expressed and regulated, as well as the expression and regulation of enzyme cofactors and substrates.

KW - A549

KW - Interleukin-1β interferon-γ

KW - Synergy

KW - Tumor necrosis factor-α

UR - http://www.scopus.com/inward/record.url?scp=0032856881&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032856881&partnerID=8YFLogxK

U2 - 10.1006/niox.1999.0242

DO - 10.1006/niox.1999.0242

M3 - Article

C2 - 10444374

AN - SCOPUS:0032856881

VL - 3

SP - 348

EP - 357

JO - Nitric Oxide - Biology and Chemistry

JF - Nitric Oxide - Biology and Chemistry

SN - 1089-8603

IS - 4

ER -