Universität zu Köln

Knobloch, Juergen, Sibbing, Bernhard, Jungck, David, Lin, Yingfeng, Urban, Katja, Stoelben, Erich, Strauch, Justus and Koch, Andrea (2010). Resveratrol Impairs the Release of Steroid-Resistant Inflammatory Cytokines from Human Airway Smooth Muscle Cells in Chronic Obstructive Pulmonary Disease. J. Pharmacol. Exp. Ther., 335 (3). S. 788 - 799. BETHESDA: AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS. ISSN 1521-0103

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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 alpha (TNF alpha), dexamethasone, and/or resveratrol was measured via enzyme-linked immunosorbent as-say and compared between nonsmokers (NS), smokers without COPD (S), and smokers with COPD (all n = 10). In response to TNF alpha, 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 TNF alpha-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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Knobloch, Juergen UNSPECIFIED UNSPECIFIED UNSPECIFIED Sibbing, Bernhard UNSPECIFIED UNSPECIFIED UNSPECIFIED Jungck, David UNSPECIFIED UNSPECIFIED UNSPECIFIED Lin, Yingfeng UNSPECIFIED UNSPECIFIED UNSPECIFIED Urban, Katja UNSPECIFIED UNSPECIFIED UNSPECIFIED Stoelben, Erich UNSPECIFIED UNSPECIFIED UNSPECIFIED Strauch, Justus UNSPECIFIED UNSPECIFIED UNSPECIFIED Koch, Andrea UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-491774
DOI:	10.1124/jpet.110.166843
Journal or Publication Title:	J. Pharmacol. Exp. Ther.
Volume:	335
Number:	3
Page Range:	S. 788 - 799
Date:	2010
Publisher:	AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
Place of Publication:	BETHESDA
ISSN:	1521-0103
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language HUMAN ALVEOLAR MACROPHAGES; COLONY-STIMULATING FACTOR; ENDOTHELIAL GROWTH-FACTOR; MOLECULAR-MECHANISMS; INHIBITION; COPD; LUNG; DEXAMETHASONE; EXPRESSION; CORTICOSTEROIDS Multiple languages Pharmacology & Pharmacy Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/49177