scholarly journals Lanthanum Chloride Inhibits LPS Mediated Expressions of Pro-Inflammatory Cytokines and Adhesion Molecules in HUVECs: Involvement of NF-κB-Jmjd3 Signaling

2017 ◽  
Vol 42 (5) ◽  
pp. 1713-1724 ◽  
Author(s):  
Xia Chen ◽  
Min Xiu ◽  
Juanjuan Xing ◽  
Shaoqing Yu ◽  
Dinghong Min ◽  
...  
Keyword(s):  
Dna Binding ◽  
Inflammatory Cytokines ◽  
Adhesion Molecule ◽  
Inflammatory Cytokine ◽  
Nuclear Translocation ◽  
Binding Activity ◽  
Promoter Regions ◽  
Dna Binding Activity ◽  
Tnf Α ◽  
Pro Inflammatory Cytokines

Background/Aims: To investigate the regulation of LaCl3 on lipopolysaccharides (LPS)-induced pro-inflammatory cytokines and adhesion molecules in human umbilical vein endothelial cells (HUVECs). Methods: Primary cultured HUVECs were pretreated with 2.5 µM LaCl3 for 30 min followed by 1 µg/ml LPS for 2 h. Pro-inflammatory cytokine and adhesion molecule expressions were determined by real-time RT-PCR and ELISA. NF-κB/p65 nuclear translocation was examined by immunofluorescence and immuno-blot, and its DNA-binding activity was measured by chemiluminescence. Recruitment of NF-κB/p65, Jmjd3, and H3K27me3 to gene promoter regions was determined by ChIP-qPCR. Results: LaCl3 exhibited no cytotoxic effects to primary HUVECs at concentrations ≤ 50 µM. LPS-mediated TNF-α, IL-1β, IL-6, MMP-9, and ICAM-1 production, nuclear translocation, and DNA-binding activity of NF-κB/p65, as well as Jmjd3 expression, were all reduced significantly by LaCl3. Furthermore, LaCl3 treatment significantly impaired LPS-induced enrichment of NF-κB/p65 to the promoter regions of TNF-α, MMP-9, IL-1β, ICAM-1, and IL-6; and of Jmjd3 to the promoter regions of TNF-α, MMP-9, IL-1β, and IL-6. H3K27me3 abundance in the promoter regions of TNF-α and ICAM-1 increased significantly in following LaCl3 treatment. Conclusion: LaCl3 inhibits pro-inflammatory cytokine and adhesion molecule expressions induced by LPS in HUVECs. NF-κB and histone demethylase Jmjd3 are involved in this effect.

Fas-associated death-domain protein inhibits TNF-α mediated NF-κB activation in cardiomyocytes

2005 ◽  
Vol 289 (5) ◽  
pp. H2073-H2080 ◽  
Author(s):  
Wei Chao ◽  
Yan Shen ◽  
Ling Li ◽  
Huailong Zhao ◽  
Steffen E. Meiler ◽  
...  
Keyword(s):  
Gene Transfer ◽  
Dna Binding ◽  
Nuclear Translocation ◽  
Binding Activity ◽  
Death Domain ◽  
Dna Binding Activity ◽  
Iκb Kinase ◽  
Tnf Α ◽  
Domain Protein

Fas-associated death-domain protein (FADD) is an adaptor molecule that links death receptors to caspase-8 in many cell types including cardiomyocytes (CMs). Although FADD has previously been reported to play an important role in CM apoptosis, the effect of FADD on CM NF-κB signaling, which is a proinflammatory pathway, has not been delineated. To investigate the role of FADD in CM NF-κB activation, we utilized adenoviral gene transfer of wild-type FADD and a truncation mutant that lacks the death-effector domain (FADD-DED) in rat CMs in vitro TNF-α activated NF-κB in CMs as demonstrated by phosphorylation and degradation of inhibitory-κB (IκB)-α-enhanced nuclear p65 and NF-κB DNA-binding activity as well as increased mRNA for the NF-κB-dependent adhesion molecule VCAM-1 (19 ± 4.1-fold) as measured by quantitative RT-PCR. Gene transfer of FADD inhibited TNF-α-induced IκB-α phosphorylation, decreased p65 nuclear translocation and NF-κB DNA-binding activity, and reduced VCAM-1 transcript levels by 53–65%. Interestingly, FADD-DED exhibited a similar but weaker inhibitory effect on NF-κB activation. The effects of FADD on NF-κB were cell-type specific. FADD expression also inhibited TNF-α-mediated NF-κB activation in human endothelial cells but not in rat pulmonary artery smooth muscle cells. In contrast, FADD expression actually activated NF-κB in human embryonic kidney (HEK)-293 cells. In CMs, FADD inhibited NF-κB activation as well as phosphorylation of IκB-α and IκB kinase (IKK)-β in response to cytokine stimulation or expression of the upstream kinases NF-κB-inducing kinase and IKK-β. These data demonstrate that FADD inhibits NF-κB activation in CMs, and this inhibition likely occurs at the level of phosphorylation and activation of IKK-β.

Inhibition of Pro-Inflammatory Cytokine Secretion by Select Antioxidants in Human Coronary Artery Endothelial Cells

2020 ◽  
Vol 90 (1-2) ◽  
pp. 103-112 ◽  
Author(s):  
Michael J. Haas ◽  
Marilu Jurado-Flores ◽  
Ramadan Hammoud ◽  
Victoria Feng ◽  
Krista Gonzales ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Ascorbic Acid ◽  
Coronary Artery ◽  
Inflammatory Cytokines ◽  
Inflammatory Cytokine ◽  
Culture Media ◽  
Cytokine Secretion ◽  
Human Coronary Artery ◽  
Tnf Α ◽  
Pro Inflammatory Cytokines

Abstract. Inflammatory and oxidative stress in endothelial cells are implicated in the pathogenesis of premature atherosclerosis in diabetes. To determine whether high-dextrose concentrations induce the expression of pro-inflammatory cytokines, human coronary artery endothelial cells (HCAEC) were exposed to either 5.5 or 27.5 mM dextrose for 24-hours and interleukin-1β (IL-1β), interleukin-2 (IL-2), interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor α (TNF α) levels were measured by enzyme immunoassays. To determine the effect of antioxidants on inflammatory cytokine secretion, cells were also treated with α-tocopherol, ascorbic acid, and the glutathione peroxidase mimetic ebselen. Only the concentration of IL-1β in culture media from cells exposed to 27.5 mM dextrose increased relative to cells maintained in 5.5 mM dextrose. Treatment with α-tocopherol (10, 100, and 1,000 μM) and ascorbic acid (15, 150, and 1,500 μM) at the same time that the dextrose was added reduced IL-1β, IL-6, and IL-8 levels in culture media from cells maintained at 5.5 mM dextrose but had no effect on IL-1β, IL-6, and IL-8 levels in cells exposed to 27.5 mM dextrose. However, ebselen treatment reduced IL-1β, IL-6, and IL-8 levels in cells maintained in either 5.5 or 27.5 mM dextrose. IL-2 and TNF α concentrations in culture media were below the limit of detection under all experimental conditions studied suggesting that these cells may not synthesize detectable quantities of these cytokines. These results suggest that dextrose at certain concentrations may increase IL-1β levels and that antioxidants have differential effects on suppressing the secretion of pro-inflammatory cytokines in HCAEC.

scholarly journals P0527AROLE OF PROMOTING INFLAMMATION OF KLF6 IN ACUTE KIDNEY INURY

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Dan Li ◽  
Chenyu Li ◽  
Yan Xu
Keyword(s):  
Inflammatory Cytokines ◽  
Inflammatory Cytokine ◽  
Ischemia Reperfusion ◽  
Kidney Injury ◽  
Tnf Α ◽  
Public Dataset ◽  
Anti Inflammatory ◽  
Anti Inflammatory Cytokine ◽  
Pro Inflammatory Cytokines

Abstract Background and Aims Acute kidney injury (AKI), commonly appeared in cardiac arrest, surgery and kidney transplantation which involved in ischemia-reperfusion (IR) injury of kidney. However, the mechanisms underlying inflammatory response in IR AKI is still unclear. Method Public dataset showed kruppel-like factor 6 (KLF6) was significantly highly expressed (P<0.05) in AKI, implies KLF6 might be associated with AKI. To evaluate the mechanism of KLF6 on IR AKI, 30 rats were randomly divided into sham and IR group, and were sacrificed at 0 h, 3 h, 6 h, 12 h or 24 h after IR. Results The results showed KLF6 expression was peaking at 6 h after IR, and the expression of pro-inflammatory cytokines MCP-1 and TNF-α were increased both in serum and kidney tissues after IR, while anti-inflammatory cytokine IL-10 was decreased after IR. Furthermore, in vitro results showed KLF6 knock-down reduced the pro-inflammatory cytokines expression and increased the anti-inflammatory cytokines expression. Conclusion These results suggest that (1) KLF6 might be a novel biomarker for early diagnosis of AKI and (2) targeting KLF6 expression may offer novel strategies to protect kidneys from IR AKI Figure KLF6, AKI, Control Inflammation

scholarly journals Methylation of STAT6 Modulates STAT6 Phosphorylation, Nuclear Translocation, and DNA-Binding Activity

2004 ◽  
Vol 172 (11) ◽  
pp. 6744-6750 ◽  
Author(s):  
Weiguo Chen ◽  
Michael O. Daines ◽  
Gurjit K. Khurana Hershey
Keyword(s):  
Dna Binding ◽  
Nuclear Translocation ◽  
Binding Activity ◽  
Dna Binding Activity

Upregulated Long Non-coding RNA ALMS1-IT1 Promotes Neuroinflammation by Activating NF-κB Signaling in Ischemic Cerebral Injury

2021 ◽  
Vol 27 ◽  
Author(s):  
Peng Lu ◽  
Ye Zhang ◽  
Huanjiang Niu ◽  
Yirong Wang
Keyword(s):  
Inflammatory Cytokines ◽  
Nuclear Translocation ◽  
Cell Model ◽  
Intrathecal Injection ◽  
Cerebral Injury ◽  
Aberrant Expression ◽  
Tnf Α ◽  
Neuro Inflammation ◽  
Pro Inflammatory Cytokines ◽  
Brain Tissues

Background: ALMS1-IT1, a recently identified lncRNA, has been proven to play a crucial role in regulating tumor progression and predicting the survival time of tumor patients. Data analysis from the Human Body Map (HBM) revealed that ALMS1-IT1 is expressed mainly in brain tissues. Methods: In this study, the role of ALMS1-IT in regulating neuro-inflammation and functional recovery was investigated after ischemic cerebral damage. To this end, the rat model of transient middle cerebral artery occlusion (tMCAO) was constructed, the cell model of oxygen-glucose deprivation (OGD) was established using BV2 microglial cells, and the aberrant expression of ALMS1-IT1 was assessed in brain tissues. After ALMS1-IT1 knockdown through intrathecal injection of Lv-shALMS1-IT1, neuro-inflammatory response and functional tests including a modified neurological severity score (mNSS) and a foot-fault test were assessed. Results: The level of ALMS1-IT1 was promptly enhanced at 12 hours (h) following MCAO, peaking at 48 h, and remaining high at day 14 compared to the sham group. Pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) were increased after MCAO, whereas ALMS1-IT1 inhibition suppressed the expression of IL-1β, IL-6 and TNF-α in MCAO rats. The results from mNSS and foot-fault test showed that ALMS1-IT1 knockdown significantly improved spatial learning and sensorimotor function of MCAO rats. Mechanistically, ALMS1-IT1 knockdown suppressed the activation of NF-κB signaling in vitro and in vivo, as evidenced by decreased p65 expression and p65 nuclear translocation. ALMS1-IT1 overexpression facilitated pro-inflammatory cytokines expression in microglia, whereas the effect was blocked by treatment with JSH-23 (a specific NF-κB inhibitor). Conclusions: These data demonstrated that ALMS1-IT1 inhibition improved neurological function of MCAO rats, at least in part by repressing NF-κB-dependent neuro-inflammation.

Effects of chronic ethanol consumption on cytokine regulation of liver regeneration

1998 ◽  
Vol 275 (4) ◽  
pp. G696-G704 ◽  
Author(s):  
Shi Qi Yang ◽  
Hui Zhi Lin ◽  
Ming Yin ◽  
Jeffrey H. Albrecht ◽  
Anna Mae Diehl
Keyword(s):  
Dna Binding ◽  
Liver Regeneration ◽  
Binding Activity ◽  
Chronic Ethanol ◽  
Cyclin D3 ◽  
Hepatocyte Proliferation ◽  
Ethanol Ingestion ◽  
Dna Binding Activity ◽  
Chronic Ethanol Consumption ◽  
Tnf Α

Ethanol ingestion may interrupt the proregenerative signal transduction that is initiated by injury-related cytokines such as tumor necrosis factor (TNF)-α and TNF-α- inducible cytokines including interleukin (IL)-6. To test this theory, liver regeneration, TNF-α and IL-6 expression, and cytokine-regulated prereplicative events were compared in ethanol-fed rats and isocalorically fed controls after 70% partial hepatectomy (PH). Ethanol feeding inhibits hepatocyte replication and recovery of liver mass after PH but generally promotes induction of both cytokines in the liver and extrahepatic tissues (i.e., white adipose tissue). Cytokine-regulated events that occur early in the prereplicative period are influenced differentially. TNF-α-dependent increases in hepatic nuclear factor-κB (NF-κB) p50 and p65 expression and DNA binding activity are prevented, whereas IL-6-dependent inductions of hepatic Stat-3 phosphorylation and DNA binding activity occur normally. In contrast, events (e.g., induction of cyclin D1, cdk-1, cyclin D3, and p53 mRNA) that occur at the end of the prereplicative period are uniformly inhibited. These findings indicate that chronic ethanol ingestion arrests the regenerative process during the prereplicative period and demonstrate that increased TNF-α, IL-6 and Stat-3 are not sufficient to assure hepatocyte proliferation after PH.

scholarly journals The protective effect of trimetazidine against cisplatin-induced nephrotoxicity in rats

2016 ◽  
Vol 94 (7) ◽  
pp. 745-751 ◽  
Author(s):  
Nagla A. El-Sherbeeny ◽  
Ghalia M. Attia
Keyword(s):  
Oxidative Stress ◽  
Dna Binding ◽  
Protective Effect ◽  
Kidney Function ◽  
Structural Changes ◽  
Binding Activity ◽  
Significant Deterioration ◽  
Necrosis Factor Alpha ◽  
Dna Binding Activity ◽  
Tnf Α

Nephrotoxicity is a dose-limiting side effect of cisplatin (CSP). The study investigated the possible protective role of trimetazidine (TMZ) against CSP-induced nephrotoxicity in rats. Rats were divided into four groups; control, TMZ, CSP, and CSP + TMZ. The CSP group showed significant deterioration in kidney function with structural changes in the form of interstitial hemorrhage, glomeruli shrinkage and peritublar capillary congestion, tubular cells vacuolation, pyknosis, shedding and necrosis, and inflammatory cell infiltrates, all indicating renal damage. CSP also caused a significant increase in the lipid peroxidation marker malondialdehyde (MDA) levels, renal nuclear factor kappa B (NF-κB) DNA-binding activity and protein expression, and tumor necrosis factor alpha (TNF-α) and IL-6 levels. Treatment with TMZ before and after CSP injection produced significant improvement of kidney function and histopathology. TMZ treatment also significantly attenuated CSP-induced oxidative stress and suppressed elevated levels of TNF-α and IL-6 and NF-κB expression and its DNA-binding activity caused by CSP administration. TMZ has a protective effect against CSP-induced nephrotoxicity mediated by reduction of oxidative stress and attenuation of CSP-induced inflammation.

scholarly journals Transcriptional Control of the Mycobacterial embCAB Operon by PknH through a Regulatory Protein, EmbR, In Vivo

2006 ◽  
Vol 188 (8) ◽  
pp. 2936-2944 ◽  
Author(s):  
Kirti Sharma ◽  
Meetu Gupta ◽  
Monika Pathak ◽  
Nidhi Gupta ◽  
Anil Koul ◽  
...  
Keyword(s):  
Dna Binding ◽  
Transcriptional Control ◽  
Regulatory Protein ◽  
Binding Activity ◽  
In Vivo Studies ◽  
Promoter Regions ◽  
Signaling Mechanism ◽  
Dna Binding Activity

ABSTRACT EmbR, a putative transcriptional regulator from Mycobacterium tuberculosis, is homologous to the OmpR class of transcriptional regulators that possess winged helix-turn-helix DNA binding motifs. In contrast to other OmpR-like response regulators that are usually phosphorylated and controlled by histidine kinases, EmbR was recently shown to be phosphorylated by the cognate mycobacterial serine/threonine kinase PknH. Despite the in vitro evidence of phosphorylation and interaction between the kinase and regulator, the physiological function of the PknH-EmbR pair is still unknown. We identify the embCAB operon encoding arabinosyltransferases in M. tuberculosis as the cellular target of EmbR. Phosphorylation of EmbR enhances its DNA binding activity towards promoter regions of embCAB genes. In vivo studies involving expression of PknH in Mycobacterium smegmatis established its positive regulatory effect on transcription of the embCAB operon via phosphorylation of EmbR. Interestingly, increased transcription of embC, catalyzing arabinosylation of lipomannan (LM) to lipoarabinomannan (LAM), results in a high LAM/LM ratio, which in turn is a crucial factor in mycobacterial virulence. The PknH-mediated increase in the transcription of embAB genes significantly alters resistance to ethambutol, a frontline antituberculosis drug known to target embAB genes. These findings and in vivo upregulation of PknH inside the host macrophages suggest a functionally relevant signaling mechanism involving the PknH-EmbR-embCAB system.

scholarly journals The Effects of New Zealand Grown Ginseng Fractions on Cytokine Production from Human Monocytic THP-1 Cells

Molecules ◽  
2021 ◽  
Vol 26 (4) ◽  
pp. 1158
Author(s):  
Wei Chen ◽  
Prabhu Balan ◽  
David G. Popovich
Keyword(s):  
New Zealand ◽  
Inflammatory Cytokines ◽  
Transforming Growth Factor Beta ◽  
Inflammatory Cytokine ◽  
Transforming Growth Factor ◽  
Enzyme Linked Immunosorbent Assay ◽  
High Dose ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Pro Inflammatory Cytokines

Pro-inflammatory cytokines and anti-inflammatory cytokines are important mediators that regulate the inflammatory response in inflammation-related diseases. The aim of this study is to evaluate different New Zealand (NZ)-grown ginseng fractions on the productions of pro-inflammatory and anti-inflammatory cytokines in human monocytic THP-1 cells. Four NZ-grown ginseng fractions, including total ginseng extract (TGE), non-ginsenoside fraction extract (NGE), high-polar ginsenoside fraction extract (HPG), and less-polar ginsenoside fraction extract (LPG), were prepared and the ginsenoside compositions of extracts were analyzed by HPLC using 19 ginsenoside reference standards. The THP-1 cells were pre-treated with different concentrations of TGE, NGE, HPG, and LPG, and were then stimulated with lipopolysaccharide (LPS). The levels of pro-inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8), and anti-inflammatory cytokines, such as interleukin-10 (IL-10), and transforming growth factor beta-1 (TGF-β1), were determined by enzyme-linked immunosorbent assay (ELISA). TGE at 400 µg/mL significantly inhibited LPS-induced TNF-α and IL-6 productions. NGE did not show any effects on inflammatory secretion except inhibited IL-6 production at a high dose. Furthermore, LPG displayed a stronger effect than HPG on inhibiting pro-inflammatory cytokine (TNF-α, IL-1β, and IL-6) productions. Particularly, 100 µg/mL LPG not only significantly inhibited the production of pro-inflammatory cytokines TNF-α, IL-1β, and IL-6, but also remarkably enhanced the production of anti-inflammatory cytokine IL-10. NZ-grown ginseng exhibited anti-inflammatory effects in vitro, which is mainly attributed to ginsenoside fractions (particularly less-polar ginsenosides) rather than non-saponin fractions.

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