title: Resveratrol attenuates the release of inflammatory cytokines from human bronchial smooth muscle cells exposed to lipoteichoic acid in chronic obstructive pulmonary disease.
abstract: During bacterial infections, pathogen-associated molecular patterns (PAMPs) induce cytokine/chemokine release in immunoactive cells. This increases corticosteroid-resistant airway inflammation in chronic obstructive pulmonary disease (COPD) and leads to exacerbations. Anti-inflammatory therapies other than corticosteroids are required and resveratrol is currently under discussion. Resveratrol is an activator of sirtuins, which are class III histone deacetylases (HDACs). We suggested that human airway smooth muscle cells (HASMCs) release COPD-associated cytokines/chemokines in response to lipoteichoic acid (LTA), a major PAMP of gram-positive bacteria and that resveratrol is superior to the corticosteroid dexamethasone in suppressing these cytokines/chemokines. Cultivated HASMCs of patients with COPD were pre-incubated with resveratrol or dexamethasone before stimulation with LTA. CCL2, GM-CSF, IL-6 and IL-8 were analysed in culture supernatants by enzyme-linked immunosorbent assay. Drug effects were investigated in the absence and presence of trichostatin A (TSA), an inhibitor of class I/II HDACs, and EX527, an inhibitor of the sirtuin SIRT1. LTA induced robust cytokine/chemokine release. Resveratrol was superior to dexamethasone in reducing CCL-2, IL-6 and IL-8 in LTA-exposed HASMCs of patients with COPD. Both drugs were equally effective in reducing GM-CSF. Resveratrol effects were partially reversed by EX527 but not by TSA. Dexamethasone effects were partially reversed by TSA but not by EX527. We conclude that HASMCs contribute to the increase in airway inflammation in COPD exacerbations caused by gram-positive bacterial infections. Our data suggest resveratrol as an alternative anti-inflammatory therapy in infection-induced COPD exacerbations. Resveratrol and corticosteroids suppress cytokine/chemokine expression through activation of SIRT1 or interaction with class I/II HDACs, respectively, in HASMCs.
authors: Department of Internal Medicine III for Pneumology, Allergology, Sleep- and Respiratory Medicine, University Hospital Bergmannsheil, Bochum, Germany.
authors: Jürgen
authors: J
authors: Knobloch
authors: Chiara
authors: C
authors: Wahl
authors: Maria
authors: M
authors: Feldmann
authors: David
authors: D
authors: Jungck
authors: Justus
authors: J
authors: Strauch
authors: Erich
authors: E
authors: Stoelben
authors: Andrea
authors: A
authors: Koch
mesh_terms: D000305:Adrenal Cortex Hormones / Q000494:pharmacology; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D002227:Carbazoles / Q000378:metabolism; D018932:Chemokine CCL2 / Q000378:metabolism; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology; D005260:Female; D006094:Gram-Positive Bacteria / Q000378:metabolism; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D006877:Hydroxamic Acids / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000378:metabolism; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy*; D012137:Respiratory System / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D000077185:Resveratrol; D056564:Sirtuin 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D013267:Stilbenes / Q000494:pharmacology*; D013682:Teichoic Acids / Q000009:adverse effects*
chemical_list: C550547:6-chloro-2,3,4,9-tetrahydro-1H-carbazole-1-carboxamide; D000305:Adrenal Cortex Hormones; D000893:Anti-Inflammatory Agents; C111835:CCL2 protein, human; D002227:Carbazoles; D018932:Chemokine CCL2; D016207:Cytokines; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D015850:Interleukin-6; D016209:Interleukin-8; D008070:Lipopolysaccharides; D013267:Stilbenes; D013682:Teichoic Acids; C012589:trichostatin A; C009900:lipoteichoic acid; D003907:Dexamethasone; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D056564:Sirtuin 1; D006655:Histone Deacetylases; D000077185:Resveratrol