June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
Dexamethasone inhibits Staphylococcus aureus -induced neutrophil extracellular pathogen-killing mechanism, possibly through toll-like receptor regulation
Author Affiliations & Notes
  • Ting Wan
    Eye Center, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
  • Yingying Zhao
    Eye Center, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
  • Fangli Fan
    Eye Center, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
  • Renjian Hu
    Eye Center, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
  • Xiuming Jin
    Eye Center, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
  • Footnotes
    Commercial Relationships   Ting Wan, None; Yingying Zhao, None; Fangli Fan, None; Renjian Hu, None; Xiuming Jin, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 4292. doi:
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      Ting Wan, Yingying Zhao, Fangli Fan, Renjian Hu, Xiuming Jin; Dexamethasone inhibits Staphylococcus aureus -induced neutrophil extracellular pathogen-killing mechanism, possibly through toll-like receptor regulation. Invest. Ophthalmol. Vis. Sci. 2017;58(8):4292.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Neutrophil extracellular traps (NETs), which are released by neutrophils in a pathogen-killing process called NETosis, are protective against the infectious diseases of human tissues including the eye. 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) by using human neutrophils in vitro.

Methods : We stimulated human neutrophils with phorbol 12-myristate 13-acetate (PMA) or Staphylococcus 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. The role of TLRs in NETs formation were also explored.

Results : DXM significantly inhibited S. aureus-induced NETosis and extracellular bacterial killing. S. aureus infection elicited significant neutrophil oxidative burst and expression of p-NF-κB (p65), but this effect was not modified by DXM. TLR2 and TLR4 agonists significantly enhanced, while blocking TLR2 and TLR4 with neutralizing antibodies significantly reduced NETs formation induced by S. aureus. However, neither the TLR5/TLR6 agonist nor the antagonist could modulate the formation of NETs induced by S. aureus. Moreover, neither DXM nor TLRs were involved in PMA-induced NETosis. Furthermore, TLR2 and TLR4 agonists rescued DXM-inhibited NETosis, and DXM could not further inhibit NETosis reduction induced by TLR2 or TLR4 antagonists, indicating that DXM may inhibit NETosis by regulating TLR2 and TLR4.

Conclusions : The mechanisms of S. aureus- and PMA-induced NETosis are different. TLR2 and TLR4, but not TLR5 or TLR6, modified S. aureus-induced NETs formation. DXM decreases NETs formation independently of oxidant production and NF-κB phosphorylation and possibly via a TLR-dependent mechanism.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

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