Streptococcus pneumoniae-Induced Oxidative Stress in Lung Epithelial Cells Depends on Pneumococcal Autolysis and Is Reversible by Resveratrol.

Streptococcus pneumoniae is the most common cause of community-acquired pneumonia worldwide. During pneumococcal pneumonia, the human airway epithelium is exposed to large amounts of H2O2 as a product of host and pathogen oxidative metabolism. Airway cells are known to be highly vulnerable to oxidant damage, but the pathophysiology of oxidative stress induced by S. pneumoniae and the role of nuclear factor erythroid 2-related factor 2 (Nrf2)-mediated antioxidant systems of the host are not well characterized. For gluthation/gluthathion disulfide analysis BEAS-2B cells, primary broncho-epithelial cells (pBEC), explanted human lung tissue and mouse lungs were infected with different S. pneumoniae strains (D39, A66, R6x, H2O2/pneumolysin/LytA- deficient mutants of R6x). Cell death was proven by LDH assay and cell viability by IL-8 ELISA. The translocation of Nrf2 and the expression of catalase were shown via Western blot. The binding of Nrf2 at the catalase promoter was analyzed by ChIP. We observed a significant induction of oxidative stress induced by S. pneumoniae in vivo, ex vivo, and in vitro. Upon stimulation, the oxidant-responsive transcription factor Nrf2 was activated, and catalase was upregulated via Nrf2. The pneumococci-induced oxidative stress was independent of S. pneumoniae-derived H2O2 and pneumolysin but depended on the pneumococcal autolysin LytA. The Nrf2 inducer resveratrol, as opposed to catalase, reversed oxidative stress in lung epithelial cells. These observations indicate a H2O2-independent induction of oxidative stress in lung epithelial cells via the release of bacterial factors of S. pneumoniae. Resveratrol might be an option for prevention of acute lung injury and inflammatory responses observed in pneumococcal pneumonia.

Zahlten J ，Kim YJ ，Doehn JM ，Pribyl T ，Hocke AC ，García P ，Hammerschmidt S ，Suttorp N ，Hippenstiel S ，Hübner RH ... -  《-》

Role of Pneumococcal Autolysin for KLF4 Expression and Chemokine Secretion in Lung Epithelium.

Zahlten J ，Herta T ，Kabus C ，Steinfeldt M ，Kershaw O ，García P ，Hocke AC ，Gruber AD ，Hübner RH ，Steinicke R ，Doehn JM ，Suttorp N ，Hippenstiel S ... -  《-》

Streptococcus pneumoniae induced c-Jun-N-terminal kinase- and AP-1 -dependent IL-8 release by lung epithelial BEAS-2B cells.

Schmeck B ，Moog K ，Zahlten J ，van Laak V ，N'Guessan PD ，Opitz B ，Rosseau S ，Suttorp N ，Hippenstiel S ... -  《RESPIRATORY RESEARCH》

Resveratrol protects primary rat hepatocytes against oxidative stress damage: activation of the Nrf2 transcription factor and augmented activities of antioxidant enzymes.

Rubiolo JA ，Mithieux G ，Vega FV 《EUROPEAN JOURNAL OF PHARMACOLOGY》

Pyruvate oxidase of Streptococcus pneumoniae contributes to pneumolysin release.

Bryant JC ，Dabbs RC ，Oswalt KL ，Brown LR ，Rosch JW ，Seo KS ，Donaldson JR ，McDaniel LS ，Thornton JA ... -  《BMC MICROBIOLOGY》