title: Dexamethasone InhibitsS. aureus-Induced Neutrophil Extracellular Pathogen-Killing Mechanism, Possibly through Toll-Like Receptor Regulation.
abstract: Neutrophils release neutrophil extracellular traps (NETs) in a pathogen-killing process called NETosis. Excessive NETs formation, however, is implicated in disease pathogenesis. Therefore, to understand how NETosis is regulated, we examined the effect of dexamethasone (DXM), an anti-inflammatory drug, on this process and the role of toll-like receptors (TLRs). We stimulated human neutrophils with phorbol 12-myristate 13-acetate (PMA) orStaphylococcus aureus(S. aureus) and quantified NETs formation. We also examined the effect of DXM on the bactericidal effect of NETs and the role of reactive oxygen species (ROS) and nuclear factor (NF)-κB in DXM-regulated NETosis. DXM significantly inhibitedS. aureus-induced NETosis and extracellular bacterial killing. ROS production and NF-κB activation were not involved in DXM-regulated NETosis. TLR2 and TLR4, but not TLR5 or TLR6, modifiedS. aureus-induced NETs formation. Neither DXM nor TLRs were involved in PMA-induced NETosis. Furthermore, TLR2 and TLR4 agonists rescued DXM-inhibited NETosis, and neither TLR2 nor TLR4 antagonists could further inhibit NETosis reduction induced by DXM, indicating that DXM may inhibit NETosis by regulating TLR2 and TLR4. In conclusion, the mechanisms ofS. aureus- and PMA-induced NETosis are different. DXM decreases NETs formation independently of oxidant production and NF-κB phosphorylation and possiblyviaa TLR-dependent mechanism.
authors.affiliation: Eye Center, Second Affiliated Hospital, School of Medicine, Zhejiang University , Hangzhou , China.
authors.forename: Ting
authors.initials: T
authors.lastname: Wan
authors.affiliation: Eye Center, Second Affiliated Hospital, School of Medicine, Zhejiang University , Hangzhou , China.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Eye Center, Second Affiliated Hospital, School of Medicine, Zhejiang University , Hangzhou , China.
authors.forename: Fangli
authors.initials: F
authors.lastname: Fan
authors.affiliation: Eye Center, Second Affiliated Hospital, School of Medicine, Zhejiang University , Hangzhou , China.
authors.forename: Renjian
authors.initials: R
authors.lastname: Hu
authors.affiliation: Eye Center, Second Affiliated Hospital, School of Medicine, Zhejiang University , Hangzhou , China.
authors.forename: Xiuming
authors.initials: X
authors.lastname: Jin
keywords: PMA; S. aureus; TLRs; dexamethasone; neutrophil extracellular traps