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Enzymatically inactive eosinophil peroxidase inhibits proinflammatory cytokine transcription and secretion by
J A Lincoln1, D L Lefkowitz, K J Grattendick
1Department of Biological Sciences, Texas Tech University, Lubbock, Texas 79409, USA.
Abstract:
The present investigators have reported previously that macrophages (Mphi) can bind either myeloperoxidase (MPO) or eosinophil peroxidase (EPO) resulting in enhanced cytotoxicity to Candida albicans. Since MPO was shown to be immunomodulatory, the present study was initiated to determine whether either EPO or partially fragmented EPO (fgEPO) also modulated cytokine secretion. Murine peritoneal Mφ simultaneously stimulated with fgEPO and one of the following, (1) LPS, (2) mannosylated bovine serum albumin (mBSA), (3) interferon-gamma (IFN-gamma), or (4) Poly I:C, demonstrated both dose- and time-dependent decreases in TNF-alpha and IL-6 and a dose-dependent decrease in IFN-alpha/beta. The mRNA levels of Mphi exposed to fgEPO and mBSA demonstrated that fgEPO modulated Mphi cytokine function by decreasing TNF-alpha and IL-6 mRNA transcripts without altering transcription of TGF-beta or GM-CSF. These results demonstrate a possible interaction between the Mphi and eosinophil that could result in reduction of inflammation.
Insights
Eosinophil peroxidase (EPO) and its fragments can modulate macrophage cytokine secretion. This interaction may reduce inflammation by decreasing key inflammatory cytokine production.
Area of Science:
- Immunology
- Cell Biology
Background:
- Macrophages (Mphi) binding myeloperoxidase (MPO) or eosinophil peroxidase (EPO) enhances cytotoxicity to Candida albicans.
- Myeloperoxidase (MPO) exhibits immunomodulatory properties.
Purpose of the Study:
- To investigate if eosinophil peroxidase (EPO) or fragmented EPO (fgEPO) modulates cytokine secretion from macrophages.
- To understand the interaction between eosinophils and macrophages in immune responses.
Main Methods:
- Murine peritoneal macrophages were stimulated with fgEPO combined with LPS, mBSA, IFN-gamma, or Poly I:C.
- Cytokine levels (TNF-alpha, IL-6, IFN-alpha/beta) and mRNA transcripts were analyzed.
- Dose- and time-dependent effects were assessed.
Main Results:
- fgEPO significantly decreased TNF-alpha and IL-6 secretion in a dose- and time-dependent manner.
- A dose-dependent decrease in IFN-alpha/beta was observed.
- fgEPO reduced TNF-alpha and IL-6 mRNA transcripts without affecting TGF-beta or GM-CSF transcription.
Conclusions:
- Fragmented eosinophil peroxidase (fgEPO) modulates macrophage cytokine function.
- This interaction between macrophages and eosinophils may lead to a reduction in inflammation.