scholarly journals Protection of cultured brain endothelial cells from cytokine-induced damage by α-melanocyte stimulating hormone

PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e4774 ◽  
Author(s):  
András Harazin ◽  
Alexandra Bocsik ◽  
Lilla Barna ◽  
András Kincses ◽  
Judit Váradi ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Rat Brain ◽  
Inflammatory Cytokines ◽  
Nuclear Translocation ◽  
Brain Endothelial Cells ◽  
Melanocyte Stimulating Hormone ◽  
Brain Pericytes ◽  
Tnf Α ◽  
Pro Inflammatory Cytokines ◽  
Stimulating Hormone

The blood–brain barrier (BBB), an interface between the systemic circulation and the nervous system, can be a target of cytokines in inflammatory conditions. Pro-inflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) induce damage in brain endothelial cells and BBB dysfunction which contribute to neuronal injury. The neuroprotective effects of α-melanocyte stimulating hormone (α-MSH) were investigated in experimental models, but there are no data related to the BBB. Based on our recent study, in which α-MSH reduced barrier dysfunction in human intestinal epithelial cells induced by TNF-α and IL-1β, we hypothesized a protective effect of α-MSH on brain endothelial cells. We examined the effect of these two pro-inflammatory cytokines, and the neuropeptide α-MSH on a culture model of the BBB, primary rat brain endothelial cells co-cultured with rat brain pericytes and glial cells. We demonstrated the expression of melanocortin-1 receptor in isolated rat brain microvessels and cultured brain endothelial cells by RT-PCR and immunohistochemistry. TNF-α and IL-1β induced cell damage, measured by impedance and MTT assay, which was attenuated by α-MSH (1 and 10 pM). The peptide inhibited the cytokine-induced increase in brain endothelial permeability, and restored the morphological changes in cellular junctions visualized by immunostaining for claudin-5 and β-catenin. Elevated production of reactive oxygen species and the nuclear translocation of NF-κB were also reduced by α-MSH in brain endothelial cells stimulated by cytokines. We demonstrated for the first time the direct beneficial effect of α-MSH on cultured brain endothelial cells, indicating that this neurohormone may be protective at the BBB.

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.

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.

scholarly journals Internalization ofStaphylococcus aureusby Bovine Endothelial Cells is Associated with the Activity State of NF-κB and Modulated by the Pro-inflammatory Cytokines TNF-α and IL-1β

2008 ◽  
Vol 67 (2) ◽  
pp. 169-176 ◽  
Author(s):  
J. Oviedo-Boyso ◽  
J. G. Barriga-Rivera ◽  
J. J. Valdez-Alarcón ◽  
A. Bravo-Patiño ◽  
A. Cárabez-Trejo ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Inflammatory Cytokines ◽  
Tnf Α ◽  
Bovine Endothelial Cells ◽  
Activity State ◽  
Pro Inflammatory Cytokines

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.

scholarly journals PON1 Deficiency Promotes TREM2 Pathway-Mediated Microglial Phagocytosis and Inhibits Pro-Inflammatory Cytokines Release in Vitro and in Vivo

2021 ◽  
Author(s):  
Li Zhang ◽  
Wei Dong ◽  
Yuanwu Ma ◽  
Lin Bai ◽  
Xu Zhang ◽  
...  
Keyword(s):  
Rat Brain ◽  
Inflammatory Cytokines ◽  
Paraoxonase 1 ◽  
Primary Microglia ◽  
Microglial Phagocytosis ◽  
Tnf Α ◽  
Pro Inflammatory Cytokines ◽  
Brain Tissues

Abstract Paraoxonase 1 (PON1) plays an anti-inflammatory role in the cardiovascular system. Levels of serum PON1 and polymorphisms in this gene were linked to Alzheimer disease (AD) and Parkinson disease (PD), but its function in the neuroimmune system and AD are not clear. To address this issue, we used PON1 knockout rats previously generated by our lab to investigate the role of PON1 in microglia. Knockout of PON1 in rat brain tissues protected against LPS-induced microglia activation. PON1 deficiency in rat primary microglia increased TREM2 (triggering receptor expressed in myeloid cells 2) expression, phagocytosis and IL-10 (M2-phenotype marker) release, but decreased production of pro-inflammatory cytokines such as IL-1β, IL-6, IL-12, IL-18 especially TNF-α (M1-phenotype markers) induced by LPS. PON1 deficiency in rat primary microglia activated TREM2 pathway but decreased LPS-induced ERK activation. The phagocytosis promoting effect of PON1 knockout could be reversed by administration of recombinant PON1 protein. The interaction between PON1 and TREM2 was verified by co-immunoprecipitation (co-IP) using rat brain tissues or over-expressed BV2 cell lysates, which might be involved in lysosomal degradation of TREM2. Furthermore, PON1 knockout may also enhance microglial phagocytosis and clearance of exogenous Aβ by an intrahippocampal injection and decrease the transcription of cytokines such as IL-1β, IL-6 and TNF-α in vivo. These results suggest an inhibitory role of PON1 in microglial phagocytosis dependent on its interaction with TREM2. These findings provide novel insights into the role of PON1 in neuroinflammation and highlight TREM2 as a potential target for Alzheimer’s disease therapy.

scholarly journals Ionizing radiation enhances IL-6 and IL-8 production by human endothelial cells

1997 ◽  
Vol 6 (3) ◽  
pp. 185-193 ◽  
Author(s):  
A. Van Der Meeren ◽  
J.-M. Bertho ◽  
M. Vandamme ◽  
M.-H. Gaugler
Keyword(s):  
Endothelial Cells ◽  
Ionizing Radiation ◽  
Inflammatory Cytokines ◽  
Umbilical Vein ◽  
Cell Lysates ◽  
Tnf Α ◽  
Umbilical Vein Endothelial Cells ◽  
Dose Dependent Increase ◽  
Dose Dependent ◽  
Pro Inflammatory Cytokines

Irradiation exposure is known to induce an inflammatory reaction. Endothelial cells play a crucial role both in the inflammatory process and in radiation damage. Therefore, supernatants and cell lysates of60Co-irradiated human umbilical vein endothelial cells (HUVEC) have been assessed for the presence of pro-inflammatory cytokines. After gamma irradiation, interleukin (IL)-1α, IL-1β and tumor necrosis factor (TNF)-α remained undetectable in both cell supernatants and cell lysates. However, a dose-dependent increase in the production of IL-6 and IL-8 has been demonstrated up to 6 days after exposure. These data indicate that the pro-inflammatory cytokines IL-6 and IL-8 may be involved in the inflammatory response of vascular endothelium induced by exposure to ionizing radiation.

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