HDAC6 inhibitor promotes reactive oxygen species-meditated clearance of Staphylococcus aureus in macrophage.

Autor: Yimiti M; Department of Laboratory Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.; College of Health Sciences and Technology, Shanghai Jiao Tong University School of Medicine, Shanghai, China., Fei X; Department of Laboratory Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.; College of Health Sciences and Technology, Shanghai Jiao Tong University School of Medicine, Shanghai, China., Yang H; Department of Laboratory Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.; College of Health Sciences and Technology, Shanghai Jiao Tong University School of Medicine, Shanghai, China., Yang X; Department of Laboratory Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.; College of Health Sciences and Technology, Shanghai Jiao Tong University School of Medicine, Shanghai, China., Li S; Department of Laboratory Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.; College of Health Sciences and Technology, Shanghai Jiao Tong University School of Medicine, Shanghai, China., Tuoheniyazi H; Department of Laboratory Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.; College of Health Sciences and Technology, Shanghai Jiao Tong University School of Medicine, Shanghai, China., Liu D; Department of Laboratory Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.; College of Health Sciences and Technology, Shanghai Jiao Tong University School of Medicine, Shanghai, China., Ma J; Department of Laboratory Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.; College of Health Sciences and Technology, Shanghai Jiao Tong University School of Medicine, Shanghai, China., Xie J; Department of Pathology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China., Zheng J; Blood Transfusion Department, Qilu Hospital of Shandong University Dezhou Hospital, Dezhou, Shandong, China., Song Z; Department of Laboratory Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.; College of Health Sciences and Technology, Shanghai Jiao Tong University School of Medicine, Shanghai, China., Li Q; Department of Laboratory Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.; College of Health Sciences and Technology, Shanghai Jiao Tong University School of Medicine, Shanghai, China., Xu D; Department of Laboratory Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.; College of Health Sciences and Technology, Shanghai Jiao Tong University School of Medicine, Shanghai, China., Zhao Y; Department of Laboratory Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.; College of Health Sciences and Technology, Shanghai Jiao Tong University School of Medicine, Shanghai, China., Gu Z; Department of Laboratory Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.; Department of Laboratory Medicine, Ruijin-Hainan Hospital, Shanghai Jiao Tong University School of Medicine (Hainan Boao Research Hospital), Qionghai, Hainan, China.
Jazyk: angličtina
Zdroj: Clinical and experimental pharmacology & physiology [Clin Exp Pharmacol Physiol] 2024 Jun; Vol. 51 (6), pp. e13866.
DOI: 10.1111/1440-1681.13866
Abstrakt: Staphylococcus aureus (S. aureus) pneumonia has become an increasingly important public health problem. Recent evidence suggests that epigenetic modifications are critical in the host immune defence against pathogen infection. In this study, we found that S. aureus infection induces the expression of histone deacetylase 6 (HDAC6) in a dose-dependent manner. Furthermore, by using a S. aureus pneumonia mouse model, we showed that the HDAC6 inhibitor, tubastatin A, demonstrates a protective effect in S. aureus pneumonia, decreasing the mortality and destruction of lung architecture, reducing the bacterial burden in the lungs and inhibiting inflammatory responses. Mechanistic studies in primary bone marrow-derived macrophages demonstrated that the HDAC6 inhibitors, tubastatin A and tubacin, reduced the intracellular bacterial load by promoting bacterial clearance rather than regulating phagocytosis. Finally, N-acetyl-L- cysteine, a widely used reactive oxygen species (ROS) scavenger, antagonized ROS production and significantly inhibited tubastatin A-induced S. aureus clearance. These findings demonstrate that HDAC6 inhibitors promote the bactericidal activity of macrophages by inducing ROS, an important host factor for S. aureus clearance and production. Our study identified HDAC6 as a suitable epigenetic modification target for preventing S. aureus infection, and tubastatin A as a useful compound in treating S. aureus pneumonia.
(© 2024 John Wiley & Sons Australia, Ltd.)
Databáze: MEDLINE
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