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Inflammation Research

, Volume 65, Issue 2, pp 151–159 | Cite as

Myeloperoxidase negatively regulates the expression of proinflammatory cytokines and chemokines by zymosan-induced mouse neutrophils

  • Daiki Endo
  • Takayuki Saito
  • Yu Umeki
  • Kazuo Suzuki
  • Yasuaki ArataniEmail author
Original Research Paper

Abstract

Objective

We have previously reported that myeloperoxidase-deficient (MPO−/−) neutrophils produce greater amounts of macrophage inflammatory protein-2 (MIP-2) upon in vitro stimulation with zymosan than wild-type neutrophils. This study aimed to examine the effect of MPO deficiency on the expression of other cytokines and chemokines.

Methods

Wild-type and MPO−/− neutrophils isolated from peritoneal cavity were stimulated with zymosan in vitro. Secretion of MIP-1α, MIP-1β, interleukin (IL)-1α, IL-1β, and tumor necrosis factor (TNF)-α by neutrophils was quantified by ELISA. mRNA expression in the neutrophils was analyzed by real-time reverse transcription-PCR, and the phosphorylation of extracellular-signal regulated kinase (ERK) 1/2 and p38 mitogen activated protein kinase (MAPK) in neutrophils was analyzed by western blot. For in vivo studies, mice were inoculated with zymosan intranasally, and the levels of these cytokines and chemokines were measured in the lungs.

Results

The MPO−/− neutrophils stimulated by zymosan expressed and secreted significantly higher levels of MIP-1α, MIP-1β, IL-1α, IL-1β, and TNF-α than the stimulated wild-type cells. Expression of all of these inflammatory mediators was blocked by pre-treatment with BAY11-7082, U0126, and SB203580, which are inhibitors of nuclear factor (NF)-κB, ERK1/2, and p38 MAPK, respectively. Enhanced expression of these inflammatory mediators is associated with elevated activation of ERK1/2 in stimulated MPO−/− neutrophils. In vivo, MPO−/− mice had significantly higher numbers of alveolar neutrophils and increased production of MIP-1α, MIP-1β, IL-1α, IL-1β, and TNF-α relative to the responses seen in wild-type mice within 24 h of zymosan administration.

Conclusion

MPO deficiency upregulates the expression of several proinflammatory cytokines and chemokines in mouse neutrophils.

Keywords

Myeloperoxidase Neutrophil Cytokine Chemokine Zymosan 

Notes

Acknowledgments

This work was supported in part by JSPS KAKENHI Grant number 26450446.

Compliance with ethical standards

Conflicts of interest

The authors report no conflicts of interest.

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Copyright information

© Springer Basel 2015

Authors and Affiliations

  • Daiki Endo
    • 1
  • Takayuki Saito
    • 1
  • Yu Umeki
    • 1
  • Kazuo Suzuki
    • 2
  • Yasuaki Aratani
    • 1
    Email author
  1. 1.Graduate School of NanobioscienceYokohama City UniversityKanazawaJapan
  2. 2.Department of Health Protection, Graduate School of Medicine, Japan Asia International Institute of Infectious Disease ControlTeikyo UniversityTokyoJapan

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