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Resveratrol Attenuates the Release of Inflammatory Cytokines from Human Bronchial Smooth Muscle Cells Exposed to Lipoteichoic Acid in Chronic Obstructive Pulmonary Disease
Author(s) -
Knobloch Jürgen,
Wahl Chiara,
Feldmann Maria,
Jungck David,
Strauch Justus,
Stoelben Erich,
Koch Andrea
Publication year - 2014
Publication title -
basic and clinical pharmacology and toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.805
H-Index - 90
eISSN - 1742-7843
pISSN - 1742-7835
DOI - 10.1111/bcpt.12129
Subject(s) - resveratrol , lipoteichoic acid , chemokine , inflammation , pharmacology , medicine , copd , dexamethasone , immunology , trichostatin a , cytokine , proinflammatory cytokine , microbiology and biotechnology , chemistry , histone deacetylase , biochemistry , biology , staphylococcus aureus , histone , bacteria , gene , genetics
During bacterial infections, pathogen‐associated molecular patterns ( PAMP s) 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 ( HDAC s). We suggested that human airway smooth muscle cells ( HASMC s) 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 HASMC s of patients with COPD were pre‐incubated with resveratrol or dexamethasone before stimulation with LTA . CCL 2, 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 HDAC s, and EX 527, an inhibitor of the sirtuin SIRT 1. LTA induced robust cytokine/chemokine release. Resveratrol was superior to dexamethasone in reducing CCL ‐2, IL ‐6 and IL ‐8 in LTA ‐exposed HASMC s of patients with COPD . Both drugs were equally effective in reducing GM ‐ CSF . Resveratrol effects were partially reversed by EX 527 but not by TSA . Dexamethasone effects were partially reversed by TSA but not by EX 527. We conclude that HASMC s 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 SIRT 1 or interaction with class I/ II HDAC s, respectively, in HASMC s.