Up-regulation of DcR3 in microbial toxins-stimulated HUVECs involves NF-\u03baB signalling

Yanqiang Hou,Yang Liu,Hongwei Chen,Xiaoli Lou,Dongyu Liang

doi:10.1186/s12858-018-0102-z

Yanqiang Hou, Yang Liu + Show 3 more

Open Access

https://doi.org/10.1186/s12858-018-0102-z

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Abstract

BackgroundSepsis is a severe condition characterised by the body’s systemic inflammatory response to infection. The specific sepsis-related biomarkers should be used in clinical diagnosis, therapeutic response monitoring, rational use of antibiotics, and prognosis (risk stratification), etc.ResultsIn this study, we investigated the expression level of Decoy Receptor 3 (DcR3) and the mechanism of high expression in sepsis patients. Septic cell model experiments were performed by treating human umbilical vein endothelial cells (HUVECs) and Jurkat cells with lipopolysaccharide (LPS), lipoteichoic acid (LTA) and zymosan, respectively. SP600125, SB203580 and ammonium pyrrolidinedithiocarbamate (PDTC) were used to inhibit JNK1/2, p38MAPK and NF-κB signalling pathways in septic cell model, respectively. These results showed that DcR3 levels were higher in sepsis group than control. DcR3 mRNA and protein levels in HUVECs were increased following treatment with LPS, LTA and zymosan, and also increased in Jurkat cells treated by LPS, but not by LTA or zymosan. When HUVECs were treated with the NF-κB inhibitor PDTC, DcR3 expression was decreased compared with controls. However, SP600125 and SB203580 had no effect on DcR3 mRNA or protein levels.ConclusionsThe results indicated that DcR3 secretion proceeded through the NF-κB signalling pathway in HUVECs.

Highlights

Sepsis is a severe condition characterised by the body’s systemic inflammatory response to infection
ELISA and western blotting confirmed the same patterns in Decoy Receptor 3 (DcR3) protein levels in human umbilical vein endothelial cells (HUVECs) and Jurkat cells co-incubated with LPS, lipoteichoic acid (LTA) or Zymosan for 24 h (Fig. 2b, c, d)
ELISA and western-blot assays confirmed the same patterns in DcR3 protein levels (inhibition by PDTC but not SB203580 or SP600125 (Fig. 4). These results demonstrated that the NF-κB signalling pathway is involved in endogenous DcR3 expression in HUVECs stimulated by LPS, LTA and zymosan (Fig. 5)

Summary

Introduction

Sepsis is a severe condition characterised by the body’s systemic inflammatory response to infection. The specific sepsis-related biomarkers should be used in clinical diagnosis, therapeutic response monitoring, rational use of antibiotics, and prognosis (risk stratification), etc. Sepsis is a condition characterised by the body’s inflammatory response to infection, and it is diagnosed where there is evidence of systemic inflammation in addition to confirmed or suspected bloodstream infection. The yearly incidence of sepsis is 300 cases per 100,000 and has been increasing years. The known presence of specific biomarkers during the response to an infectious insult makes possible the potential clinical use of such biomarkers in screening, diagnosis, prognosis (risk stratification), therapeutic response monitoring, and rational use of antibiotics (determination of adequate treatment length, for example). New biomarkers related to infectious diseases have been tested during recent years, but few has overcome the rigorous testing required for use in clinical practice [3,4,5]

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