sFasL-mediated induction of neutrophil activation in patients with type 2 diabetes mellitus

Sona Margaryan; Agata Witkowicz; Arsen Arakelyan; Anna Partyka; Lidia Karabon; Gayane Manukyan

doi:10.1371/journal.pone.0201087

sFasL-mediated induction of neutrophil activation in patients with type 2 diabetes mellitus

PLoS One. 2018 Jul 19;13(7):e0201087. doi: 10.1371/journal.pone.0201087. eCollection 2018.

Authors

Sona Margaryan^{1

2}, Agata Witkowicz³, Arsen Arakelyan^{1

4}, Anna Partyka³, Lidia Karabon³, Gayane Manukyan^{1

2}

Affiliations

¹ Russian-Armenian University, Yerevan, Armenia.
² Laboratory of Molecular and Cellular Immunology, Institute of Molecular Biology, Yerevan, Armenia.
³ Department of Experimental Therapy, L. Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland.
⁴ Bioinformatics Group, Institute of Molecular Biology, Yerevan, Armenia.

Abstract

Fas/Fas ligand system was shown to be related to insulin resistance and type 2 diabetes mellitus (T2DM). However, the role of soluble Fas ligand (sFasL) in functioning of immune cells in type 2 diabetes mellitus (T2DM) has not been studied yet. The aim of the present study was to determine in vitro effects of sFasL on neutrophil activation and apoptosis. We demonstrate here that sFasL exhibited proinflammatory effect and induced mRNA levels of caspase-1, NF-κB, IL-1β and CD18 expression. At the same time, sFasL induced reactive oxygen species (ROS) production. Activation of caspase-1 activity abolished sFasL-dependent apoptosis, and suppressed Fas expression and mRNA levels of caspase-3 in neutrophils from T2DM patients. Collectively, our findings identify a novel proinflammatory role of sFasL in T2DM neutrophils that is dependent of caspase activity. Thus, sFasL enhances inflammatory response of neutrophils from T2DM patients without increasing apoptosis suggesting its triggering role in T2DM inflammation.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Apoptosis / physiology
Cells, Cultured
Diabetes Mellitus, Type 2 / blood*
Diabetes Mellitus, Type 2 / immunology*
Fas Ligand Protein / administration & dosage
Fas Ligand Protein / metabolism*
Female
Humans
Interleukin-1beta / metabolism
Interleukin-8 / metabolism
Male
Middle Aged
Neutrophil Activation*
Neutrophils / immunology*
RNA, Messenger / metabolism

Substances

CXCL8 protein, human
FASLG protein, human
Fas Ligand Protein
IL1B protein, human
Interleukin-1beta
Interleukin-8
RNA, Messenger

Grants and funding

This work was supported by the U-GENE, 7. PR UE PEOPLE Marie Curie International Research Staff Exchange Scheme (IRSES) number 319010, and Wroclaw Centre of Biotechnology, programme The Leading National Research Centre (KNOW) for years 2014-2018, as well as Russian-Armenian University within the framework of the grant of the Ministry of Education and Science of the Russian Federation. The cost of publication was covered by Wroclaw Centre of Biotechnology, programme The Leading National Research Centre (KNOW) for years 2014-2018.