scholarly journals TACE/ADAM17–TNF-α Pathway in Rat Cortical Cultures after Exposure to Oxygen–Glucose Deprivation or Glutamate

2002 ◽  
Vol 22 (5) ◽  
pp. 576-585 ◽  
Author(s):  
Olivia Hurtado ◽  
Ignacio Lizasoain ◽  
Paz Fernández-Tomé ◽  
Alberto Álvarez-Barrientos ◽  
Juan C. Leza ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Glucose Deprivation ◽  
Microglial Cells ◽  
Oxygen Glucose Deprivation ◽  
Tnf Α ◽  
Cortical Cultures ◽  
Rat Forebrain ◽  
Necrosis Factor ◽  
Mixed Cortical Cultures

The role of the tumor necrosis factor (TNF)-α convertase (TACE/ADAM17) in the adult nervous system remains poorly understood. The authors have previously demonstrated that TACE is upregulated in rat forebrain slices exposed to oxygen–glucose deprivation (OGD). They have now used rat mixed cortical cultures exposed to OGD or glutamate to study (1) TACE expression and localization, and (2) the effects of TNF-α release on cell viability. OGD- or glutamate-caused TNF-α release, an effect that was blocked by the TACE inhibitor BB3103 (BB) (0.1–1 μmol/L; control: 1.67 ± 0.59; OGD: 6.59 ± 1.52; glutamate: 3.38 ± 0.66; OGD ± BB0.1: 3.23 ± 0.67; OGD ± BB1: 1.33 ± 0.22 pg/mL, n = 6, P < 0.05). Assay of TACE activity as well as Western blot showed that TACE expression is increased in OGD- or glutamate-exposed cells. In control cultures, TACE immunoreactivity was present in some microglial cells, whereas, after OGD or glutamate, TACE immunostaining appeared in most microglial cells and in some astrocytes. Conversely, BB3103 (0.1 μmol/L) caused apoptosis after glutamate exposure as shown by annexin and Hoechst 33342 staining and caspase-3 activity, an effect mimicked by the proteasome inhibitor MG-132 (caspase activity: glutamate: 5.1 ± 0.1; glutamate + BB: 7.8 ± 0.8; glutamate + MG: 11.9 ± 0.5 pmol · min−1 mg−1 protein, n = 4, P < 0.05), suggesting that translocation of the transcription factor NF-κB mediates TNF-α–induced antiapoptotic effect. Taken together, these data demonstrate that, in rat mixed neuronal–glial cortical cultures exposed to OGD or glutamate, (1) TACE/ADAM17 activity accounts for the majority of TNF-α shedding, (2) an increase in glial TACE expression contributes to the rise in TNF-α, and (3) TNF-α release in this setting inhibits apoptosis via activation of the transcription factor NF-κB.

scholarly journals Fluoxetine suppresses inflammatory reaction in microglia under OGD/R challenge via modulation of NF-κB signaling

2019 ◽  
Vol 39 (4) ◽  
Author(s):  
Mouli Tian ◽  
Mei Yang ◽  
Zhenjie Li ◽  
Yiru Wang ◽  
Wei Chen ◽  
...  
Keyword(s):  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Glucose Deprivation ◽  
Cell Counting ◽  
Enzyme Linked Immunosorbent Assay ◽  
Oxygen Glucose Deprivation ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Related Proteins

Abstract We aimed to investigate the anti-inflammatory role of fluoxetine, a selective serotonin reuptake inhibitor, in microglia (MG) and the mechanisms under oxygen glucose deprivation/reoxygenation (OGD/R). An OGD/R model on BV-2 cells was used for the study of microglia under ischemia/reperfusion injury in ischemic stroke. Lentiviral transfection was applied to knock down IκB-α. Enzyme-linked immunosorbent assay (ELISA) was used for detecting levels of TNF-α, IL-1β, and IL-6, and real-time PCR was used to assess the expression of IκB-α protein. Western blotting was applied to analyze NF-κB-signaling related proteins and Cell Counting Kit-8 (CCK-8) was used for assessing cell viability. Molecular docking and drug affinity responsive target stability (DARTS) assay were used for the detection of the interaction between IκB-α and fluoxetine. We found that fluoxetine decreased the levels of TNF-α, IL-1β, and IL-6 in supernatant as well as NF-κB subunits p65 and p50 in BV-2 cells under OGD/R. Fluoxetine significantly increased the level of IκB-α through the inhibition of IκB-α ubiquitylation and promoted the bonding of IκB-α and fluoxetine in BV-2 cells under OGD/R. Knocking down IκB-α attenuated the decreasing effect of TNF-α, IL-1β, and IL-6 as well as p65 and p50 in BV-2 cells under OGD/R led to by fluoxetine. In conclusion, our present study demonstrated the anti-inflammatory role of fluoxetine and its mechanisms related to the modulation of NF-κB-related signaling in MG under ischemia/reperfusion challenge.

Up-regulation of TNF-α convertase (TACE/ADAM17) after oxygen–glucose deprivation in rat forebrain slices

2001 ◽  
Vol 40 (8) ◽  
pp. 1094-1102 ◽  
Author(s):  
Olivia Hurtado ◽  
Antonio Cárdenas ◽  
Ignacio Lizasoain ◽  
Lisardo Boscá ◽  
Juan C Leza ◽  
...  
Keyword(s):  
Glucose Deprivation ◽  
Oxygen Glucose Deprivation ◽  
Tnf Α ◽  
Rat Forebrain

scholarly journals Chandipura virus dysregulates the expression of hsa-miR-21-5p to activate NF-κB in human microglial cells

2021 ◽  
Vol 28 (1) ◽  
Author(s):  
Neha Pandey ◽  
Meghana Rastogi ◽  
Sunit K. Singh
Keyword(s):  
Expression Pattern ◽  
Case Fatality ◽  
Microglial Cells ◽  
Luciferase Assay ◽  
Western India ◽  
Cellular Mirnas ◽  
Over Expression ◽  
Chandipura Virus ◽  
Tnf Α

Abstract Background Chandipura virus (CHPV) is a negative single-stranded RNA virus of the Rhabdoviridae family. CHPV infection has been reported in Central and Western India. CHPV causes acute encephalitis with a case fatality rate of 70 % and mostly affects children below 15 years of age. CHPV infection in brain leads to neuronal apoptosis and activation of the microglial cells. The microRNAs (miRNAs) are small endogenous non-coding RNA that regulate the gene expression. Viral infections perturb the expression pattern of cellular miRNAs, which may in turn affect the expression pattern of downstream genes. This study aims to investigate hsa-miR-21-5p mediated regulation of PTEN, AKT, NF-ĸBp65, IL-6, TNF-α, and IL-1β, in human microglial cells during CHPV infection. Methods To understand the role of hsa-miR-21-5p in CHPV infection, the human microglial cells were infected with CHPV (MOI-0.1). Real-time PCR, western blotting, Luciferase assay, over-expression and knockdown techniques were used to understand the role of hsa-miR-21-5p in the regulation of PTEN, AKT and, NF-ĸBp65, IL-6, TNF-α, and IL-1β in this study. Results The hsa-miR-21-5p was found to be upregulated during CHPV infection in human microglial cells. This led to the downregulation of PTEN which promoted the phosphorylation of AKT and NF-ĸBp65. Over-expression of hsa-miR-21-5p led to the decreased expression of PTEN and promoted further phosphorylation of AKT and NF-ĸBp65 in human microglial cells. However, the inhibition of hsa-miR-21-5p using hsa-miR-21-5p inhibitor restored the expression. Conclusions This study supports the role of hsa-miR-21-5p in the regulation of pro-inflammatory genes in CHPV infected human microglial cells.

scholarly journals Hypoxia-Induced S100A8 Expression Activates Microglial Inflammation and Promotes Neuronal Apoptosis

2021 ◽  
Vol 22 (3) ◽  
pp. 1205
Author(s):  
Ji Sun Ha ◽  
Hye-Rim Choi ◽  
In Sik Kim ◽  
Eun-A Kim ◽  
Sung-Woo Cho ◽  
...  
Keyword(s):  
Calcium Binding ◽  
Neuronal Apoptosis ◽  
Microglial Cells ◽  
Molecular Pattern ◽  
Extracellular Signal ◽  
Tnf Α ◽  
Cox 2 ◽  
Necrosis Factor ◽  
Microglial Inflammation ◽  
Tlr4 Receptor

S100 calcium-binding protein A8 (S100A8), a danger-associated molecular pattern, has emerged as an important mediator of the pro-inflammatory response. Some S100 proteins play a prominent role in neuroinflammatory disorders and increase the secretion of pro-inflammatory cytokines in microglial cells. The aim of this study was to determine whether S100A8 induced neuronal apoptosis during cerebral hypoxia and elucidate its mechanism of action. In this study, we reported that the S100A8 protein expression was increased in mouse neuronal and microglial cells when exposed to hypoxia, and induced neuroinflammation and neuronal apoptosis. S100A8, secreted from neurons under hypoxia, activated the secretion of tumor necrosis factor (TNF-α) and interleukin-6 (IL-6) through phosphorylation of extracellular-signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) in microglia. Also, phosphorylation of ERK via the TLR4 receptor induced the priming of the NLRP3 inflammasome. The changes in Cyclooxygenase-2 (COX-2) expression, a well-known inflammatory activator, were regulated by the S100A8 expression in microglial cells. Knockdown of S100A8 levels by using shRNA revealed that microglial S100A8 expression activated COX-2 expression, leading to neuronal apoptosis under hypoxia. These results suggested that S100A8 may be an important molecule for bidirectional microglia-neuron communication and a new therapeutic target for neurological disorders caused by microglial inflammation during hypoxia.

scholarly journals Is Inflammation a Friend or Foe for Orthodontic Treatment?: Inflammation in Orthodontically Induced Inflammatory Root Resorption and Accelerating Tooth Movement

2021 ◽  
Vol 22 (5) ◽  
pp. 2388
Author(s):  
Masaru Yamaguchi ◽  
Shinichi Fukasawa
Keyword(s):  
Inflammatory Mediators ◽  
Orthodontic Treatment ◽  
Alveolar Bone ◽  
Tooth Movement ◽  
Root Resorption ◽  
Orthodontic Tooth Movement ◽  
Tnf Α ◽  
Orthodontic Forces ◽  
Necrosis Factor

The aim of this paper is to provide a review on the role of inflammation in orthodontically induced inflammatory root resorption (OIIRR) and accelerating orthodontic tooth movement (AOTM) in orthodontic treatment. Orthodontic tooth movement (OTM) is stimulated by remodeling of the periodontal ligament (PDL) and alveolar bone. These remodeling activities and tooth displacement are involved in the occurrence of an inflammatory process in the periodontium, in response to orthodontic forces. Inflammatory mediators such as prostaglandins (PGs), interleukins (Ils; IL-1, -6, -17), the tumor necrosis factor (TNF)-α superfamily, and receptor activator of nuclear factor (RANK)/RANK ligand (RANKL)/osteoprotegerin (OPG) are increased in the PDL during OTM. OIIRR is one of the accidental symptoms, and inflammatory mediators have been detected in resorbed roots, PDL, and alveolar bone exposed to heavy orthodontic force. Therefore, these inflammatory mediators are involved with the occurrence of OIIRR during orthodontic tooth movement. On the contrary, regional accelerating phenomenon (RAP) occurs after fractures and surgery such as osteotomies or bone grafting, and bone healing is accelerated by increasing osteoclasts and osteoblasts. Recently, tooth movement after surgical procedures such as corticotomy, corticision, piezocision, and micro-osteoperforation might be accelerated by RAP, which increases the bone metabolism. Therefore, inflammation may be involved in accelerated OTM (AOTM). The knowledge of inflammation during orthodontic treatment could be used in preventing OIIRR and AOTM.

ROLE OF INTER LEUKIN 10 AND TUMOR NECROSIS FACTOR-ΑLPHA IN PANCREATITIS

2021 ◽  
pp. 14-17
Author(s):  
Mukherjee.J. R ◽  
Mukherjee. B ◽  
Roy. S ◽  
Jana. D ◽  
Bandopadhyay. S ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
General Surgery ◽  
Tumor Necrosis ◽  
Cell Injury ◽  
Gall Stone ◽  
Tnf Alpha ◽  
Tnf Α ◽  
The Mean ◽  
Necrosis Factor

Background: Pancreatic acinar cell injury triggers the synthesis and release of pro-inammatory cytokines and chemokines. The involvement of several pro-inammatory and anti-inammatory cytokines, such as in interleukin (IL)-1, IL-1β, IL-6, IL-8, IL-10, IL-18, IL-33 and tumor necrosis factor-α is involved in the pathogenesis of pancreatitis. Aim: This study aims to validate the role of activation of TNF-alpha and IL-10 as a biomaker marker in patients with Pancreatitis in Indian subcontinent.Material and methods: 50 Patients of Pancreatitis attending general surgery OPD and admitted to General Surgery department of SSKM Hospital, Kolkata, West Bengal, India were taken. Result: It was found that in alcoholic, the mean TNF - α (mean±s.d.) of the patients was 19.4027 ± 8.3275 pg/ml. In ascites, the mean TNF - α (mean±s.d.) of the patients was 19.9767 ± 2804 pg/ml. In chronic, the mean TNF - α (mean±s.d.) of the patients was 18.8533 ± 8.4674 pg/ml. In gall stone, the mean TNF - α (mean±s.d.) of the patients was 16.3421 ± 9.9499 pg/ml. In osteoarthritis, the mean TNF - α (mean±s.d.) of the patients was 12.4750 ± 8.3085 pg/ml. Distribution of mean TNF - α vs. association was not statistically signicant (p=0.7309).Conclusion: It was found that IL10 was higher in Ascites patients though it was not statistically signicant. TNF alpha was higher in Ascites patients. TNF alpha was higher in normal Pancreatitis.

The Role of Tumor Necrosis Factor-α (TNF-α) Polymorphisms in Gastric Cancer: a Meta-Analysis

2021 ◽  
Author(s):  
Maryam Gholamalizadeh ◽  
Samaneh Mirzaei Dahka ◽  
Hadi Sedigh Ebrahim-Saraie ◽  
Mohammad Esmail Akbari ◽  
Azam Pourtaheri ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Meta Analysis ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor
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