scholarly journals Hsa_circ_0000652 Aggravates Inflammation by Activation of Macrophages and Enhancement of OX40/OX40L Interaction in Ankylosing Spondylitis

Author(s):  
Minkai Song ◽  
Jiawen Gao ◽  
Tao Yan ◽  
Enguang Bi ◽  
Taixue An ◽  
...  

Circular RNAs (circRNAs) have emerged as important roles in various inflammatory processes of rheumatic diseases. However, their expression profiles and influences in the pathogenesis of ankylosing spondylitis (AS) remain unclear. In this study, we revealed the differential expression profiles of circRNAs in peripheral blood mononuclear cells (PBMCs) in AS by circRNA sequencing. We screened the differentially expressed circRNAs in AS and verified that hsa_circ_0000652 was upregulated and had potential to be a biomarker of progression. Functionally, hsa_circ_0000652 promoted proliferation and cytokine production in macrophages and inhibited apoptosis. Through dual-luciferase assays and RNA pull-down assays, we demonstrated that hsa_circ_0000652 acted as a competing endogenous RNA (ceRNA) by binding with hsa-miR-1179 and regulated OX40L, which is characterized as a co-stimulatory molecule and found to be upregulated in AS patients. As a result, hsa_circ_0000652 aggravated the inflammation in the coculture system containing CD4+ T cells and macrophages via OX40/OX40L interaction. Our findings suggest that hsa_circ_0000652 was upregulated in AS patients and may serve as a pro-inflammatory factor in macrophages and a positive regulator of OX40/OX40L by sponging hsa-miR-1179.

2013 ◽  
Vol 4 (4) ◽  
pp. 313-317 ◽  
Author(s):  
N.J. Hepburn ◽  
I. Garaiova ◽  
E.A. Williams ◽  
D.R. Michael ◽  
S. Plummer

The objective of this study was to examine the effect of daily probiotic supplementation upon the immune profile of healthy participants by the assessment of ex vivo cytokine production. Twenty healthy adult volunteers received a multi-strain probiotic supplement consisting of two strains of Lactobacillus acidophilus (CUL60 and CUL21), Bifidobacterium lactis (CUL34) and Bifidobacterium bifidum (CUL20) and fructooligosaccharide for 12 weeks. Blood samples were collected at baseline, 6 and 12 weeks. Peripheral blood mononuclear cells (PBMCs) were isolated and cultured ex vivo in the presence or absence of lipopolysaccharide and cytokine production was assessed. Postintervention, a significant decrease in the production of interleukin-6 and interleukin-1β was apparent when PBMCs were incubated in the presence of lipopolysaccharide, whilst a significant increase in IL-10 and transforning growth factor-β production was seen when the cells were incubated without an additional stimulus. This preliminary study demonstrates the potential of a multi-strain probiotic supplement to alter the immune response as demonstrated by changes in ex vivo cytokine production. Such results demonstrate the potential benefit of probiotic supplementation for healthy individuals and warrants further investigation.


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