Does Nuclear Factor-Kappa B in Peripheral Mononuclear Cells Have a Prognostic Role during Acute Necrotizing Pancreatitis in Rats

2012 ◽  
Vol 48 (1) ◽  
pp. 34-39 ◽  
Author(s):  
E. Alhan ◽  
S. Türkyılmaz ◽  
C. Erçin ◽  
B.V. Kural ◽  
D. Flinte
2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
H Liu ◽  
C G Zhu ◽  
C J Cui ◽  
Y X Cao ◽  
D I Sun ◽  
...  

Abstract Abstract Background Inflammation may play an important role in atherosclerosis in familial hypercholesterolemia (FH). Lipopolysaccharide (LPS)-nuclear factor-kappa B (NF-κB) pathway is a routine signal process activated in inflammatory status. Purpose This study aimed to examine the LPS-NF-κB axis status and the impact of lipoprotein apheresis (LA) on this pathway in patients with FH and coronary artery disease (CAD). Methods In this matched case-control study a genetically diagnosed FH cohort who presented stable CAD (n=63) was compared with 63 non-FH CAD and 63 non-FH non-CAD controls matched by sex and age. Plasma LPS levels and NF-κB activity were compared among the three groups. In addition, we studied in vitro LPS-induced interleukin-6 (IL-6) production by mononuclear cells from 16 FH cases without previous statin use and compared them with their respective matched control groups. Subsequently, these 16 FH patients underwent LA. Blood samples were taken immediately before and regularly after LA for measuring LPS and NF-κB. Results FH plus CAD had higher LPS levels and NF-κB activity than CAD and non-CAD controls (all p values <0.01). LPS-induced IL-6 production by mononuclear cells of FH plus CAD was also much higher compared with CAD and non-CAD controls (both p values <0.01). Moreover, plasma LPS levels (p<0.001) and NF-κB activity (p<0.01) were dramatically reduced after apheresis in FH patients. Conclusion Genetically confirmed FH patients with CAD had a marked activation of LPS-NF-κB axis, while LA significantly attenuated this key inflammatory pathway, suggesting that inflammation may be an important therapeutic target for FH patients.


Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Huihui Liu ◽  
Cheng-Gang Zhu ◽  
Chuan-Jue Cui ◽  
Yexuan Cao ◽  
Jinglu Jin ◽  
...  

Introduction: Inflammation may play an important role in atherosclerosis in familial hypercholesterolemia (FH). Lipopolysaccharide (LPS)-nuclear factor-kappa B (NF-κB) pathway is a routine signal process activated in inflammatory status. Hypothesis: We assessed the hypothesis that LPS-NF-κB axis is markedly activated and lipoprotein apheresis has an inhibitory effect on this pathway in patients with FH and coronary artery disease (CAD). Methods: In this matched case-control study a genetically diagnosed FH cohort who presented stable CAD (n=63) was compared with 63 non-FH CAD and 63 non-FH non-CAD controls matched by sex and age. Plasma LPS levels and NF-κB activity were compared among the three groups. In addition, we studied in vitro LPS-induced interleukin-6 production by mononuclear cells from 16 FH cases without previous statin use and compared them with their respective matched control groups. Subsequently, these 16 FH patients underwent lipoprotein apheresis. Blood samples were taken immediately before and regularly after apheresis for measuring LPS and NF-κB. Results: FH plus CAD had higher LPS levels and NF-κB activity than CAD and non-CAD controls (all p <0.01). LPS-induced interleukin-6 production by mononuclear cells of FH plus CAD was also much higher compared with CAD and non-CAD controls (both p <0.01). Moreover, plasma LPS levels ( p <0.001) and NF-κB activity ( p <0.01) were dramatically reduced after apheresis in FH patients. Conclusions: In conclusion, genetically confirmed FH patients with CAD had a marked activation of LPS-NF-κB axis, while lipoprotein apheresis significantly attenuated this key inflammatory pathway, suggesting that inflammation may be an important therapeutic target for FH patients.


Author(s):  
Alireza Farrokhian ◽  
Mahtab Miraftab ◽  
Minoo Chenari ◽  
Hossein Akbari ◽  
Hassan Nikoueinejad ◽  
...  

Osteoprotegerin (OPG), receptor activator of nuclear factor-kappa B (RANK) and receptor activator of nuclear factor-kappa B ligand (RANKL), the members of the tumor necrosis factor (TNF) family, have multiple effects on bone metabolism, endocrine functions and, as an inflammatory pathway, in the immune system. This study tried to determine the association of the OPG/RANKL/RANK axis with the severity of unstable angina (UA) as an inflammatory condition. Our study involved 50 patients with UA and 50 healthy people. Serum and peripheral blood mononuclear cells were isolated from all participants. Serum levels and gene expression of OPG, RANKL, and RANK in mononuclear cells were measured by enzyme-linked immunosorbent assay (ELISA) and real-time polymerase chain reaction (RT-PCR), respectively. For each patient with UA, the thrombolysis in myocardial infarction (TIMI) and the global registry of acute coronary events (GRACE) scores were determined to evaluate the severity of the disease. Then we analyzed the relation of OPG, RANKL, and RANK levels with TIMI and GRACE scores in patients with UA. Discriminate analysis was used to predict the combinational models of such factors on the prediction of UA. Serum levels of OPG and RANKL (p<0.001) and gene expression of RANKL (p<0.001) were significantly more in patients than those in healthy ones. No relation was seen between the OPG/RANKL/RANK axis and the severity of UA according to TIMI and GRACE scores. Our study shows that serum level, as well as gene expression of OPG/RANKL/RANK axis neither, predicts the occurrence of UA nor shows any relationship with its severity.  


2004 ◽  
Vol 56 (2) ◽  
pp. 212-218 ◽  
Author(s):  
Christian H Schroeter ◽  
Bianca Schaub ◽  
Diane R Gold ◽  
Paola J Contreras ◽  
Oscar Manrique ◽  
...  

Antioxidants ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 180 ◽  
Author(s):  
Stefanie Hofer ◽  
Simon Geisler ◽  
Rebecca Lisandrelli ◽  
Hieu Nguyen Ngoc ◽  
Markus Ganzera ◽  
...  

The flavonoid kaempferol is almost ubiquitously contained in edible and medicinal plants and exerts a broad range of interesting pharmacological activities. Interactions with central inflammatory processes can be exploited to treat or attenuate symptoms of disorders associated with chronic immune activation during infections, malignancies, and neurodegenerative or cardiovascular disorders. Many drugs, phytochemicals, and nutritional components target the catabolism of the essential amino acid tryptophan by indoleamine 2,3-dioxygenase 1 (IDO-1) for immunomodulation. We studied the effects of kaempferol by in vitro models with human peripheral blood mononuclear cells (PBMC) and THP-1 derived human myelomonocytic cell lines. Kaempferol suppressed interferon-γ dependent immunometabolic pathways: Formation of the oxidative stress biomarker neopterin and catabolism of tryptophan were inhibited dose-dependently in stimulated cells. In-silico docking studies revealed a potential interaction of kaempferol with the catalytic domain of IDO-1. Kaempferol stimulated nuclear factor kappa B (NF-κB) signaling in lipopolysaccharide (LPS)-treated THP-1 cells, thereby increasing the mRNA expression of interleukin (IL) 1 beta, tumor necrosis factor, and nuclear factor kappa B subunit 1, while IL6 was downregulated. Data suggest that concerted effects of kaempferol on multiple immunologically relevant targets are responsible for its immunomodulatory activity. However, the immunosuppressive effects may be more relevant in a T-cell dominated context.


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