scholarly journals Neutrophil extracellular trap from Kawasaki disease alter the biologic responses of PBMC

2020 ◽  
Vol 40 (9) ◽  
Author(s):  
Yang Jing ◽  
Meng Ding ◽  
Jiuyuan Fu ◽  
Yanping Xiao ◽  
Xianghua Chen ◽  
...  
Keyword(s):  
Kawasaki Disease ◽  
Mononuclear Cells ◽  
Systemic Vasculitis ◽  
Hypoxia Inducible Factor ◽  
Neutrophil Extracellular Trap ◽  
Peripheral Blood Mononuclear ◽  
Pathological Mechanism ◽  
Phosphoinositide 3 Kinase ◽  
20 Nm ◽  
Endothelial Growth Factor

Abstract Kawasaki disease (KD), also known as mucocutaneous lymph node syndrome, is an acute systemic vasculitis syndrome that mainly occurs in infants under 5 years of age. In the current manuscript, we were aiming to analyze the role of neutrophil extracellular traps (NETs) in the pathogenesis of KD, especially their interplay with peripheral blood mononuclear cells (PBMCs). Neutrophils were exposed to 20 nM phorbol myristate acetate (PMA), we found that neutrophils of KD patients were more likely to form NETs compared with healthy controls (HCs). Furthermore, PBMCs were cultured with NETs for 24 h, and we observed that NETs significantly increased the cell viability, suppressed cell apoptosis, and enhanced the pro-inflammatory cytokines production and NF-κB activation in PBMCs from KD patients. In addition, with the stimulation of NETs, the expression of vascular endothelial growth factor A (VEGF-A) and hypoxia-inducible factor-1α (HIF-1α) were increased, which were related with the pathological mechanism of KD. At last, we examined the activation of phosphoinositide 3 kinase (PI3K)/Akt signaling, and we found NETs treatment obviously enhanced the activation of PI3K and Akt. In conclusion, these findings suggested that the formation of NETs may alter the biologic responses of PBMC and affect the vascular injury in KD.

Association Between the lncRNA TDRG1 rs8506 C>T Polymorphism and Susceptibility To Kawasaki Disease in Chinese Children

2021 ◽  
Author(s):  
Jinqing Li ◽  
Kai Guo ◽  
Hongyan Yu ◽  
Yufen Xu ◽  
Chuanzi Yang ◽  
...  
Keyword(s):  
Coronary Artery ◽  
Kawasaki Disease ◽  
Systemic Vasculitis ◽  
Recessive Model ◽  
Chinese Children ◽  
Future Research ◽  
Human Testis ◽  
Non Coding Rna ◽  
Vegf Pathway ◽  
Endothelial Growth Factor

Abstract Background Kawasaki disease (KD) is an acute systemic vasculitis with unknown pathogen, and the formation of coronary artery lesions/aneurysm (CAL/CAA) is the most common sequela. Environmental and genetic factors have been suggested to be involved in the pathogenesis of KD. Human testis development related 1(TDRG1) is a newly identified long non-coding RNA (lncRNA) which stimulates the vascular endothelial growth factor (VEGF) pathway. The aim of this study was to investigate the association between genetic polymorphism of TDRG1 and the risk of KD. Methods A total of two cohorts from Guangzhou (988 KD patients and 1054 controls) and Beijing (564 KD patients and 1221 controls) were enrolled in the present study. Rs8506 of TDRG1 was chosen for TaqMan genotyping assay. Results Logistic regression suggested that lncRNA TDRG1 rs8506 C > T polymorphism was not associated with the risk of KD in both Guangzhou and Beijing cohort (dominant model and recessive model: P > 0.05). Moreover, we also did not observe a significant association between the lncRNA TDRG1 rs8506 C > T polymorphism and the risk of KD patients with different ages, gender or coronary artery outcomes in both Guangzhou and Beijing cohort. Conclusions The present study revealed that the lncRNA TDRG1 rs8506 C > T polymorphism might not be associated with susceptibility to KD in Chinese children. Future research with a larger sample size should be performed to confirm these results.

BCR/ABL induces expression of vascular endothelial growth factor and its transcriptional activator, hypoxia inducible factor-1α, through a pathway involving phosphoinositide 3-kinase and the mammalian target of rapamycin

Blood ◽  
2002 ◽  
Vol 100 (10) ◽  
pp. 3767-3775 ◽  
Author(s):  
Matthias Mayerhofer ◽  
Peter Valent ◽  
Wolfgang R. Sperr ◽  
James D. Griffin ◽  
Christian Sillaber
Keyword(s):  
Gene Expression ◽  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Mammalian Target Of Rapamycin ◽  
Hypoxia Inducible Factor ◽  
Vascular Endothelial ◽  
Vegf Gene ◽  
Vegf Mrna ◽  
Phosphoinositide 3 Kinase ◽  
Endothelial Growth Factor

Recent data suggest that vascular endothelial growth factor (VEGF), a cytokine involved in autocrine growth of tumor cells and tumor angiogenesis, is up-regulated and plays a potential role in myelogenous leukemias. In chronic myelogenous leukemia (CML), VEGF is expressed at high levels in the bone marrow and peripheral blood. We show here that the CML-associated oncogene BCR/ABL induces VEGF gene expression in growth factor–dependent Ba/F3 cells. Whereas starved cells were found to contain only baseline levels of VEGF mRNA, Ba/F3 cells induced to express BCR/ABL exhibited substantial amounts of VEGF mRNA. BCR/ABL also induced VEGF promoter activity and increased VEGF protein levels in Ba/F3 cells. Moreover, BCR/ABL was found to promote the expression of functionally active hypoxia-inducible factor-1 (HIF-1), a major transcriptional regulator of VEGF gene expression. BCR/ABL-induced VEGF gene expression was counteracted by the phosphoinositide 3-kinase (PI3-kinase) inhibitor LY294002 and rapamycin, an antagonist of mammalian target of rapamycin (mTOR), but not by inhibition of the mitogen-activated protein kinase pathway. Similarly, BCR/ABL-dependent HIF-1α expression was inhibited by the addition of LY294002 and rapamycin. Together, our data show that BCR/ABL induces VEGF- and HIF-1α gene expression through a pathway involving PI3-kinase and mTOR. BCR/ABL-induced VEGF expression may contribute to the pathogenesis and increased angiogenesis in CML.

Sign in / Sign up

Export Citation Format

Share Document