scholarly journals Intensive Statin Therapy Compromises the Adiponectin-AdipoR Pathway in the Human Monocyte-Macrophage Lineage

Stroke ◽  
2019 ◽  
Vol 50 (12) ◽  
pp. 3609-3617 ◽  
Author(s):  
Karina Gasbarrino ◽  
Anouar Hafiane ◽  
Huaien Zheng ◽  
Stella S. Daskalopoulou
Keyword(s):  
Gene Expression ◽  
Risk Factors ◽  
Cardiovascular Risk ◽  
Statin Therapy ◽  
Carotid Atherosclerosis ◽  
Human Monocyte ◽  
Intensive Statin Therapy ◽  
Macrophage Lineage

Background and Purpose— Statins are widely used for cardiovascular disease prevention through cholesterol-lowering and anti-inflammatory effects. Adiponectin, an anti-inflammatory adipokine, acts via two receptors, AdipoR1 and AdipoR2, to exert atheroprotective effects on the vasculature. We investigated whether statins can modulate the adiponectin-AdipoR pathway in the human monocyte-macrophage lineage. Methods— Monocytes were isolated from the whole blood of patients with severe carotid atherosclerosis (cross-sectional study) or from patients with cardiovascular risk factors (longitudinal study) and assessed for AdipoR1 and AdipoR2 gene expression using quantitative real-time polymerase chain reaction. In vitro, THP-1 (Tamm-Horsfall protein 1) macrophages were treated with increasing atorvastatin or rosuvastatin doses for 24- or 72-hours to determine the effect of statins on AdipoR expression and activity. Macrophage cytokine secretion (IL [interleukin]-1β, IL-10, IL-6, and TNF [tumor necrosis factor]-α) was assessed by electrochemiluminescence. Results— AdipoR1 and AdipoR2 mRNA expression on circulating monocytes from patients with carotid atherosclerosis, was significantly lower by 1.36- and 1.17-fold, respectively, in statin users versus statin-naïve patients. Specifically, patients on high doses of atorvastatin (40–80 mg) or rosuvastatin (20–40 mg) had significantly lower AdipoR gene expression versus statin-naïve patients. Similarly, in the longitudinal in vivo study, longer atorvastatin/rosuvastatin treatment (≥5 months) in patients with cardiovascular risk factors resulted in lower AdipoR gene expression on circulating monocytes versus prestatin levels. In vitro, higher statin doses and longer exposure resulted in a greater decrease in AdipoR mRNA expression and greater macrophage secretion of pro-inflammatory cytokines, IL-1β, IL-6, and TNF-α. High statin doses also reduced adiponectin’s capacity to suppress intracellular cholesteryl ester levels in oxLDL (oxidized LDL)-loaded macrophages, with rosuvastatin exhibiting higher potency than atorvastatin. Conclusions— Our in vivo and in vitro studies identified a novel pleiotropic property of statins in modulating the adiponectin-AdipoR pathway in the human monocyte-macrophage lineage, where intensive statin therapy compromised the expression and function of adiponectin and its receptors.

scholarly journals In vitro response of macrophages to ceramic scaffolds used for bone regeneration

2016 ◽  
Vol 13 (120) ◽  
pp. 20160346 ◽  
Author(s):  
Pamela L. Graney ◽  
Seyed-Iman Roohani-Esfahani ◽  
Hala Zreiqat ◽  
Kara L. Spiller
Keyword(s):  
Gene Expression ◽  
Inflammatory Response ◽  
Bone Regeneration ◽  
Bone Repair ◽  
Principal Component ◽  
Human Monocyte ◽  
Macrophage Phenotype ◽  
In Vitro Response

Macrophages, the primary cells of the inflammatory response, are major regulators of healing, and mediate both bone fracture healing and the inflammatory response to implanted biomaterials. However, their phenotypic contributions to biomaterial-mediated bone repair are incompletely understood. Therefore, we used gene expression and protein secretion analysis to investigate the interactions in vitro between primary human monocyte-derived macrophages and ceramic scaffolds that have been shown to have varying degrees of success in promoting bone regeneration in vivo . Specifically, baghdadite (Ca 3 ZrSi 2 O 9 ) and strontium–hardystonite–gahnite (Sr–Ca 2 ZnSi 2 O 7 –ZnAl 2 O 4 ) scaffolds were chosen as two materials that enhanced bone regeneration in vivo in large defects under load compared with clinically used tricalcium phosphate–hydroxyapatite (TCP–HA). Principal component analysis revealed that the scaffolds differentially regulated macrophage phenotype. Temporal changes in gene expression included shifts in markers of pro-inflammatory M1, anti-inflammatory M2a and pro-remodelling M2c macrophage phenotypes. Of note, TCP–HA scaffolds promoted upregulation of many M1-related genes and downregulation of many M2a- and M2c-related genes. Effects of the scaffolds on macrophages were attributed primarily to direct cell–scaffold interactions because of only minor changes observed in transwell culture. Ultimately, elucidating macrophage–biomaterial interactions will facilitate the design of immunomodulatory biomaterials for bone repair.

Effect of X-irradiation on gene expression of rat liver chemokines: in vivo and in vitro studies

2008 ◽  
Vol 46 (01) ◽  
Author(s):  
F Moriconi ◽  
H Christiansen ◽  
H Christiansen ◽  
N Sheikh ◽  
J Dudas ◽  
...  
Keyword(s):  
Gene Expression ◽  
Rat Liver ◽  
In Vitro Studies ◽  
X Irradiation

Vibrio harveyi virulence gene expression in vitro and in vivo during infection in black tiger shrimp Penaeus monodon

2020 ◽  
Vol 139 ◽  
pp. 153-160
Author(s):  
S Peeralil ◽  
TC Joseph ◽  
V Murugadas ◽  
PG Akhilnath ◽  
VN Sreejith ◽  
...  
Keyword(s):  
Gene Expression ◽  
Virulence Genes ◽  
Vibrio Harveyi ◽  
Penaeus Monodon ◽  
Challenge Test ◽  
Virulence Gene ◽  
Economic Losses ◽  
Virulence Gene Expression

Luminescent Vibrio harveyi is common in sea and estuarine waters. It produces several virulence factors and negatively affects larval penaeid shrimp in hatcheries, resulting in severe economic losses to shrimp aquaculture. Although V. harveyi is an important pathogen of shrimp, its pathogenicity mechanisms have yet to be completely elucidated. In the present study, isolates of V. harveyi were isolated and characterized from diseased Penaeus monodon postlarvae from hatcheries in Kerala, India, from September to December 2016. All 23 tested isolates were positive for lipase, phospholipase, caseinase, gelatinase and chitinase activity, and 3 of the isolates (MFB32, MFB71 and MFB68) showed potential for significant biofilm formation. Based on the presence of virulence genes, the isolates of V. harveyi were grouped into 6 genotypes, predominated by vhpA+ flaB+ ser+ vhh1- luxR+ vopD- vcrD+ vscN-. One isolate from each genotype was randomly selected for in vivo virulence experiments, and the LD50 ranged from 1.7 ± 0.5 × 103 to 4.1 ± 0.1 × 105 CFU ml-1. The expression of genes during the infection in postlarvae was high in 2 of the isolates (MFB12 and MFB32), consistent with the result of the challenge test. However, in MFB19, even though all genes tested were present, their expression level was very low and likely contributed to its lack of virulence. Because of the significant variation in gene expression, the presence of virulence genes alone cannot be used as a marker for pathogenicity of V. harveyi.

Evidence that gene expression of ovarian follicular tight junction proteins is regulated in vivo and in vitro in cattle

2017 ◽  
Vol 95 (3) ◽  
pp. 1313 ◽  
Author(s):  
L. Zhang ◽  
L. F. Schütz ◽  
C. L. Robinson ◽  
M. L. Totty ◽  
L. J. Spicer
Keyword(s):  
Gene Expression ◽  
Tight Junction ◽  
Tight Junction Proteins ◽  
Junction Proteins

Subnuclear compartmentalization of sequence-specific transcription factors and regulation of eukaryotic gene expression

2005 ◽  
Vol 83 (4) ◽  
pp. 535-547 ◽  
Author(s):  
Gareth N Corry ◽  
D Alan Underhill
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Transcription Factors ◽  
Transcriptional Activation ◽  
Current Knowledge ◽  
Nuclear Architecture ◽  
Subnuclear Localization ◽  
Modular Structures

To date, the majority of the research regarding eukaryotic transcription factors has focused on characterizing their function primarily through in vitro methods. These studies have revealed that transcription factors are essentially modular structures, containing separate regions that participate in such activities as DNA binding, protein–protein interaction, and transcriptional activation or repression. To fully comprehend the behavior of a given transcription factor, however, these domains must be analyzed in the context of the entire protein, and in certain cases the context of a multiprotein complex. Furthermore, it must be appreciated that transcription factors function in the nucleus, where they must contend with a variety of factors, including the nuclear architecture, chromatin domains, chromosome territories, and cell-cycle-associated processes. Recent examinations of transcription factors in the nucleus have clarified the behavior of these proteins in vivo and have increased our understanding of how gene expression is regulated in eukaryotes. Here, we review the current knowledge regarding sequence-specific transcription factor compartmentalization within the nucleus and discuss its impact on the regulation of such processes as activation or repression of gene expression and interaction with coregulatory factors.Key words: transcription, subnuclear localization, chromatin, gene expression, nuclear architecture.

scholarly journals CircFAM13B promotes the proliferation of hepatocellular carcinoma by sponging miR-212, upregulating E2F5 expression and activating the P53 pathway

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Ying Xie ◽  
Xiaofeng Hang ◽  
Wensheng Xu ◽  
Jing Gu ◽  
Yuanjing Zhang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Hepatocellular Carcinoma ◽  
Gene Expression Omnibus ◽  
Differentially Expressed ◽  
In Vivo Studies ◽  
Circular Rnas ◽  
Novel Target ◽  
Underlying Mechanisms

Abstract Background Most of the biological functions of circular RNAs (circRNAs) and the potential underlying mechanisms in hepatocellular carcinoma (HCC) have not yet been discovered. Methods In this study, using circRNA expression data from HCC tumor tissues and adjacent tissues from the Gene Expression Omnibus database, we identified out differentially expressed circRNAs and verified them by qRT-PCT. Functional experiments were performed to evaluate the effects of circFAM13B in HCC in vitro and in vivo. Results We found that circFAM13B was the most significantly differentially expressed circRNA in HCC tissue. Subsequently, in vitro and in vivo studies also demonstrated that circFAM13B promoted the proliferation of HCC. Further studies revealed that circFAM13B, a sponge of miR-212, is involved in the regulation of E2F5 gene expression by competitively binding to miR-212, inhibits the activation of the P53 signalling pathway, and promotes the proliferation of HCC cells. Conclusions Our findings revealed the mechanism underlying the regulatory role played by circFAM13B, miR-212 and E2F5 in HCC. This study provides a new theoretical basis and novel target for the clinical prevention and treatment of HCC.

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