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Research ArticleGastrointestinal, Hepatic, Pulmonary, and Renal

Resveratrol Impairs the Release of Steroid-Resistant Inflammatory Cytokines from Human Airway Smooth Muscle Cells in Chronic Obstructive Pulmonary Disease

Jürgen Knobloch, Bernhard Sibbing, David Jungck, Yingfeng Lin, Katja Urban, Erich Stoelben, Justus Strauch and Andrea Koch
Journal of Pharmacology and Experimental Therapeutics December 2010, 335 (3) 788-798; DOI: https://doi.org/10.1124/jpet.110.166843
Jürgen Knobloch
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Bernhard Sibbing
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David Jungck
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Yingfeng Lin
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Katja Urban
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Erich Stoelben
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Justus Strauch
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Andrea Koch
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Abstract

Chronic obstructive pulmonary disease (COPD) therapy is complicated by corticosteroid resistance of the interleukin 8 (IL-8)-dependent and granulocyte macrophage-colony stimulating factor (GM-CSF)-dependent chronic airway inflammation, for whose establishment human airway smooth muscle cells (HASMCs) might be crucial. It is unclear whether the release of inflammatory mediators from HASMCs is modulated by cigarette smoking and is refractory to corticosteroids in COPD. Resveratrol, an antiaging drug with protective effects against lung cancer, might be an alternative to corticosteroids in COPD therapy. Vascular endothelial growth factor (VEGF) might offer protection from developing emphysema. We tested the following hypotheses for HASMCs: 1) smoking with or without airway obstruction modulates IL-8, GM-CSF, and VEGF release; and 2) corticosteroids, but not resveratrol, fail to inhibit cytokine release in COPD. Cytokine release from HASMCs exposed to tumor necrosis factor α (TNFα), dexamethasone, and/or resveratrol was measured via enzyme-linked immunosorbent assay and compared between nonsmokers (NS), smokers without COPD (S), and smokers with COPD (all n = 10). In response to TNFα, IL-8 release was increased, but GM-CSF and VEGF release was decreased in S and COPD compared with NS. Dexamethasone and resveratrol inhibited concentration-dependently TNFα-induced IL-8, GM-CSF, and VEGF release. For IL-8 and GM-CSF efficiency of dexamethasone was NS > S > COPD. That of resveratrol was NS = S = COPD for IL-8 and NS = S < COPD for GM-CSF. For VEGF the efficiency of dexamethasone was NS = S = COPD, and that of resveratrol was NS = S > COPD. All resveratrol effects were partially based on p38 mitogen-activated protein kinase blockade. In conclusion, smoking modulates cytokine release from HASMCs. Corticosteroid refractoriness of HASMCs in COPD is cytokine-dependent. Resveratrol might be superior to corticosteroids in COPD therapy, because it more efficiently reduces the release of inflammatory mediators and has limited effects on VEGF in COPD.

Footnotes

  • The study was financially supported by the Moritz-Stiftung, Cologne, Germany [Grant 36460040].

  • Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.

    doi:10.1124/jpet.110.166843.

  • ABBREVIATIONS:

    COPD
    chronic obstructive pulmonary disease
    AM
    alveolar macrophage
    ASMC
    airway smooth muscle cell
    HASMC
    human ASMC
    ET-1
    endothelin-1
    GM-CSF
    granulocyte macrophage-colony stimulating factor
    HDAC
    histone deacetylase
    IL
    interleukin
    MAPK
    mitogen-activated protein kinase
    NF-κB
    nuclear factor κB
    NS
    nonsmokers
    S
    smokers without COPD
    TNFα
    tumor necrosis factor α
    VEGF
    vascular endothelial growth factor
    SB203580
    4-[4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-1H-imidazol-5-yl]pyridine
    RT-PCR
    reverse transcription-polymerase chain reaction
    ELISA
    enzyme-linked immunosorbent assay
    ANOVA
    analysis of variance
    GOLD
    Global Initiative for Chronic Obstructive Lung Disease
    GAPDH
    glyceraldehyde-3-phosphate dehydrogenase
    FVC
    forced vital capacity
    FEV1
    forced expiratory volume in 1 s.

  • Received February 2, 2010.
  • Accepted August 25, 2010.
  • Copyright © 2010 by The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 384 (2)
Journal of Pharmacology and Experimental Therapeutics
Vol. 384, Issue 2
1 Feb 2023
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Research ArticleGastrointestinal, Hepatic, Pulmonary, and Renal

Resveratrol Impairs the Release of Steroid-Resistant Inflammatory Cytokines from Human Airway Smooth Muscle Cells in Chronic Obstructive Pulmonary Disease

Jürgen Knobloch, Bernhard Sibbing, David Jungck, Yingfeng Lin, Katja Urban, Erich Stoelben, Justus Strauch and Andrea Koch
Journal of Pharmacology and Experimental Therapeutics December 1, 2010, 335 (3) 788-798; DOI: https://doi.org/10.1124/jpet.110.166843

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Research ArticleGastrointestinal, Hepatic, Pulmonary, and Renal

Resveratrol Impairs the Release of Steroid-Resistant Inflammatory Cytokines from Human Airway Smooth Muscle Cells in Chronic Obstructive Pulmonary Disease

Jürgen Knobloch, Bernhard Sibbing, David Jungck, Yingfeng Lin, Katja Urban, Erich Stoelben, Justus Strauch and Andrea Koch
Journal of Pharmacology and Experimental Therapeutics December 1, 2010, 335 (3) 788-798; DOI: https://doi.org/10.1124/jpet.110.166843
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