RT Journal Article
SR Electronic
T1 Heme oxygenase–1 induced by quercetin attenuates TGF-β-stimulated collagen production in fibroblasts
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP p2003
VO 38
IS Suppl 55
A1 Tsutomu Kawabe
A1 Toshinobu Nakamura
A1 Miyoko Matsushima
A1 Yuta Hayashi
A1 Masataka Shibasaki
A1 Kazuyoshi Imaizumi
A1 Naozumi Hashimoto
A1 Kaoru Shimokata
A1 Yoshinori Hasegawa
YR 2011
UL http://erj.ersjournals.com/content/38/Suppl_55/p2003.abstract
AB Quercetin is a flavonoid with a wide variety of cytoprotective and modulatory functions. Heme oxygenase–1 (HO-1) is an inducible enzyme. Its reaction product, carbon monoxide (CO), confers cellular protection in a number of conditions and diseases associated with oxidative or inflammatory lung injury. Furthermore, quercetin was reported to be a potent inducer of HO-1 in several cell types. We hypothesized that quercetin suppresses the production of collagen in fibroblasts via the induction of HO-1. Here, we showed that quercetin suppresses transforming growth factor–β (TGF-β) induced collagen production in NIH3T3 cells and in normal human lung fibroblasts. This suppressive effect of quercetin was mediated by quercetin-induced HO-1. The suppression of collagen production was conferred by the reaction product of HO-1, CO, but not by bilirubin. Furthermore, the translocation of the nuclear factor E2–related factor–2 (Nrf2), an important transcription factor that regulates the expression of HO-1 from the cytoplasm to the nuclei, was demonstrated in NIH3T3 cells by exposure to quercetin. Assessment of the signal transduction pathway involved in TGF-β signaling showed that quercetin stimulated the Smad and mitogen-activated protein kinase pathway to varying degrees. Our results demonstrate that quercetin exerts suppressive effects on the expression of collagen by the induction of HO-1. Idiopathic pulmonary fibrosis is the most lethal diffuse fibrosing lung disease, and is characterized by the deposition of extracellular matrix. Quercetin or its derivatives, which effectively induced HO-1, will lead to new therapeutic strategies for promoting antifibrotic therapy in respiratory diseases.