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

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

Sona Margaryan  1   2 , Agata Witkowicz  3 , Arsen Arakelyan  1   4 , Anna Partyka  3 , Lidia Karabon  3 , Gayane Manukyan  1   2
Affiliations

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

Sona Margaryan et al. PLoS One. .

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.

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Baseline mRNA levels of candidate genes in neutrophils from T2DM patients (T2DM) and healthy controls (healthy) measured by quantitative RT-PCR.
All gene expressions are relative to β2M. Data are represented as scatterplots. Error bars are means ± SEM for each group.
Fig 2
Fig 2. Relative mRNA levels of candidate genes in neutrophils T2DM patients (T2DM) and healthy controls (healthy) after 3-hour culture with media alone as a control (Ctl) or sFasL (150ng/ml) measured by quantitative RT-PCR.
All gene expressions are relative to β2M. Data are represented as scatterplots. Error bars are means ± SEM for each group (*P<0.05, **P<0.01).
Fig 3
Fig 3
The influence of sFasL on neutrophils from T2DM patients (T2DM) and healthy controls (H) after 3-hour culture with media alone as a control (Ctl) or sFasL (150ng/ml) measured by flow cytometry: A) Percentage of CD62L and expression levels of CD18; B) Apoptotic rates of circulating neutrophils measured using Annexin V and Propidium iodide (PI); C) Percentage of Fas positive cells; D) Median fluorescence intensity (MFI) of ROS measured using dihydrorhodamine 123.
Fig 4
Fig 4. Secreted levels of cytokines IL-1β and IL-8 from T2DM patients (T2DM) and healthy controls (H) after 3-hour culture of isolated neutrophils with media alone as a control (Ctl) or sFasL (150ng/ml) measured by ELISA.
Data are represented as scatterplots. Error bars are means ± SEM for each group (*P<0.05, **P<0.01).
See this image and copyright information in PMC

References

    1. Engström G, Stavenow L, Hedblad B, Lind P, Eriksson KF, Janzon L, et al. Inflammation-sensitive plasma proteins, diabetes, and mortality of myocardial infarction and stroke: a population-based study. Diabetes. 2003;52(2):442–447. - PubMed
    1. Pickup JC. Inflammation and activated innate immunity in the pathogenesis of type 2 diabetes mellitus. Diabetes Care. 2004;27(3):813–823. - PubMed
    1. Esser N, Legrand-Poels S, Piette J, Scheen AJ, Paquot N. Inflammation as a link between obesity, metabolic syndrome and type 2 diabetes. Diabetes Res Clin Pract. 2014;105(2):141–150. 10.1016/j.diabres.2014.04.006 - DOI - PubMed
    1. Butler AE, Janson J, Bonner-Weir S, Ritzel R, Rizza RA, Butler PC. Beta-cell deficit and increased beta-cell apoptosis in humans with type 2 diabetes. Diabetes. 2003;52(1):102–110. - PubMed
    1. Mandrup-Poulsen T. beta-cell apoptosis: Stimuli and signaling. Diabetes. 2001;50 Suppl 1:S58–63. - PubMed

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