Combined modulation of the mesangial machinery for monocyte recruitment by inhibition of NF-κB

2001 ◽  
Vol 281 (6) ◽  
pp. C1881-C1888 ◽  
Author(s):  
Alma Zernecke ◽  
Kim S. C. Weber ◽  
Christian Weber
Keyword(s):  
Adhesion Molecule ◽  
Mesangial Cells ◽  
Nuclear Factor Κb ◽  
Pharmacological Intervention ◽  
Monocyte Chemoattractant Protein 1 ◽  
Intracellular Adhesion Molecule ◽  
Tnf Α ◽  
Monocyte Chemotaxis ◽  
Or Gene ◽  
Factor Α

The activation of nuclear factor-κB (NF-κB) is required for the induction of many of the adhesion molecules and chemokines involved in the inflammatory leukocyte recruitment to the kidney. Here we studied the effects of NF-κB inhibition on the machinery crucial for monocyte infiltration of the glomerulus during inflammation. In mesangial cells (MC), the protease inhibitors MG-132 and N-α-tosyl-l-lysine chloromethyl ketone or adenoviral overexpression of IκB-α prevented the complete IκB-α degradation following tumor necrosis factor-α (TNF-α) stimulation. This resulted in a marked inhibition of TNF-α-induced expression of mRNA and protein for the immunoglobulin molecules intracellular adhesion molecule-1 and vascular cell adhesion molecule-1 and the chemokines growth-related oncogene-α, monocyte chemoattractant protein-1, interleukin-8, or fractalkine in MC. Finally, the inhibition of IκB-α degradation or IκB-α overexpression suppressed the chemokine-induced transendothelial monocyte chemotaxis toward MC and the chemokine-triggered firm adhesion of monocytic cells to MC. The inhibition of NF-κB by pharmacological intervention or gene transfer may present a multimodal approach to control the machinery propagating inflammatory recruitment of monocytes during glomerular disease.

scholarly journals Resveratrol prevents TNF-α-induced VCAM-1 and ICAM-1 upregulation in endothelial progenitor cells via reduction of NF-κB activation

2020 ◽  
Vol 48 (9) ◽  
pp. 030006052094513
Author(s):  
Yefei Zhang ◽  
Huahua Liu ◽  
Weiliang Tang ◽  
Qiongya Qiu ◽  
Jiahao Peng
Keyword(s):  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Adhesion Molecule ◽  
Nuclear Factor Κb ◽  
Intercellular Adhesion Molecule ◽  
Adhesion Assay ◽  
Intercellular Adhesion Molecule 1 ◽  
Endothelial Progenitor ◽  
Tnf Α ◽  
Factor Α

Objective To assess the effects of resveratrol (RSV) on expression of adhesion molecules in endothelial progenitor cells (EPCs) following tumor necrosis factor-α (TNF-α) stimulation. Methods EPCs were treated with RSV and stimulated with TNF-α. A mononuclear cell (MNC) adhesion assay was used to assess the effects of RSV on TNF-α-induced MNC adhesion. Vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1) and E-selectin expression levels and nuclear factor κB (NF-κB) activation were assessed by immunoblotting. Results MNC adhesion to TNF-α-treated EPCs and VCAM-1/ICAM-1/E-selectin levels in EPCs were increased following TNF-α stimulation and decreased following RSV treatment. TNF-α enhanced NF-κB inhibitor α (IκB-α) phosphorylation in the cytosol as well as nuclear NF-κB p65 levels, both of which were decreased by RSV. Conclusions These findings provide new insights into RSV’s anti-inflammatory and anti-atherosclerotic effects. RSV’s mechanism of action might involve downregulation of VCAM-1, ICAM-1 and E-selectin by partial blockade of TNF-α-induced NF-κB activation and IκB-α phosphorylation in EPCs.

scholarly journals Tanshinone II A Attenuates TNF-α-Induced Expression of VCAM-1 and ICAM-1 in Endothelial Progenitor Cells by Blocking Activation of NF-κB

2016 ◽  
Vol 40 (1-2) ◽  
pp. 195-206 ◽  
Author(s):  
Jin-Xiu Yang ◽  
Yan-Yun Pan ◽  
Jun-Hua Ge ◽  
Bin Chen ◽  
Wei Mao ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Adhesion Molecule ◽  
Inflammatory Cells ◽  
Nuclear Factor Κb ◽  
Tanshinone Iia ◽  
Adhesion Assay ◽  
Endothelial Progenitor ◽  
Tnf Α ◽  
Factor Α

Background/Aims: Tanshinone IIA (Tan IIA) is effective in the treatment of inflammation and atherosclerosis. The adhesion of inflammatory cells to vascular endothelium plays important role in atherogenic processes. This study examined the effects of Tan IIA on expression of adhesion molecules in tumor necrosis factor-α (TNF-α)-induced endothelial progenitor cells (EPCs). Methods: EPCs were pretreated with Tan IIA and stimulated with TNF-α. Mononuclear cell (MNC) adhesion assay was performed to assess the effects of Tan IIA on TNF-α-induced MNC adhesion. Expression of vascular cell adhesion molecule-1 (VCAM-1)/intracellular adhesion molecule-1 (ICAM-1) and activation of Nuclear factor κB (NF-κB) signaling pathway were measured. Results: The results showed that the adhesion of MNCs to TNF-α-induced EPCs and expression of VCAM-1/ICAM-1 in EPCs were promoted by TNF-α, which were reduced by Tan IIA. TNF-α increased the amount of phosphorylation of NF-κB, IκB-α and IKKα/β in cytosolic fractions and NF-κB p65 in nucleus, while Tan IIA reduced its amount. Conclusion: This study demonstrated a novel mechanism for the anti-inflammatory/anti-atherosclerotic activity of Tan IIA, which may involve down-regulation of VCAM-1 and ICAM-1 through partial blockage of TNF-α-induced NF-κB activation and IκB-α phosphorylation by the inhibition of IKKα/β pathway in EPCs.

Παθοφυσιολογία της αντίδρασης του ενδοθηλίου μετά από αγγειοπλαστική νεφρικής αρτηρίας

2014 ◽  
Author(s):  
Κυριακή Ταβερναράκη
Keyword(s):  
Adhesion Molecule ◽  
Intercellular Adhesion Molecule ◽  
Vascular Cell Adhesion ◽  
Intercellular Adhesion Molecule 1 ◽  
Monocyte Chemoattractant Protein 1 ◽  
Monocyte Chemoattractant ◽  
Tnf Α ◽  
Factor Α ◽  
Cell Adhesion Molecule 1 ◽  
Necrosis Factor

Σκοπός:Για τη μελέτη του παθοφυσιολογικού μηχανισμού αντίδρασης του τοιχώματος της νεφρικής αρτηρίας που εκλύεται κατά την αγγειοπλαστική με τοποθέτηση stent πραγματοποιήθηκε ποσοτικός προσδιορισμός έξι διαφορετικών παραγόντων φλεγμονής -μεσολαβητών (κυτοκίνες) στον ορό αίματος ασθενών που υποβλήθηκαν σε αυτήν την μέθοδο. Απώτερος σκοπός της μελέτης, μέσω της αξιολόγησης των διαφορών στις συγκεντρώσεις των μεσολαβητών σε ασθενείς που εμφάνισαν ή όχι επαναστένωση του αγγείου, είναι η αναγνώριση καποιού παράγοντα φλεγμονής που θα αποτελέσει δείκτη πρόβλεψης της επαναστένωσης με στόχο την πρόληψη αυτής.Υλικό - Μέθοδος:Μελετήθηκαν είκοσι δύο ασθενείς (17 άνδρες, μέσος όρος ηλικίας 66 έτη), με στένωση στην έκφυση της νεφρικής αρτηρίας και μή καλώς ρυθμιζόμενη υπέρταση, οι οποίοι υποβλήθησαν σε αγγειοπλαστική νεφρικής αρτηρίας με τοποθέτηση stent. Στους ασθενείς αυτούς πραγματοποιήθηκαν αιμοληψίες σε τρεις διαφορετικούς χρόνους: αμέσως πριν την αγγειοπλαστική (baseline), 24 ώρες και 6 μήνες μετά την αγγειοπλαστική και μετρήθηκαν στον ορό τους οι εξής μεσολαβητές: (1) Παράγοντας Νέκρωσης Όγκου-α (Tumor necrosis factor-α, TNF-α), (2) Ιντερλευκίνη 6 (Interleukin-6, IL-6), (3) Πρωτεΐνη χημειοτακτική για τα μονοκύτταρα τύπου-1 (Monocyte Chemoattractant protein-1, MCP-1), (4) Διακυτταρικό μόριο προσκόλλησης-1 (Intercellular adhesion molecule-1, ICAM-1), (5) Μόριο προσκόλλησης αγγειακών κυττάρων-1 (Vascular cell Adhesion Molecule-1, VCAM-1) και (6) Παράγοντας RANTES (Regulated upon Activation Normal T-cell Expressed presumed Secreted). Στους έξι μήνες μετά την αγγειοπλαστική πραγματοποιήθηκε έχρωμο Doppler υπερηχογράφημα και καταγράφηκε η ανάπτυξη ή όχι επαναστένωσης εντός του stent. Επιπλέον, αξιολογήθηκαν οι διαφορές της συγκέντρωσης αυτών σε ασθενείς που εμφάνισαν επαναστένωση της νεφρικής αρτηρίας στους 6 μήνες μετά την αγειοπλαστική συγκριτικά με αυτούς που δεν εμφάνισαν επαναστένωση.Αποτελέσματα:Η συγκέντρωση της ΙL-6 αυξήθηκε σημαντικά 24 ώρες μετά την αγγειοπλαστική (8.3 pg/mL ± 1.24 vs 2.76 pg/mL ± 1.27 τιμές baseline), ενώ στους 6 μήνες μετά επέστρεψε στις προ την επέμβαση τιμές (2.6 pg/mL ± 1.77) (Ρ<.0001). Δεν σημειώθηκαν στατιστικά σημαντικές διαφορές στις συγκεντρώσεις των υπολοίπων μεσολαβητών σε κανέναν από τους τρεις χρόνους. Επίσης, βρέθηκε πως η συγκέντρωση της ΙL-6 τόσο πρίν την αγγειοπλαστική όσο και 6 μήνες μετά την αγγειοπλαστική ήταν σημαντικά υψηλότερη στους ασθενείς που ανάπτυξαν επαναστένωση (8.13 pg/mL ± 4 vs 0.75 pg/mL ± 0.47 [P,.005] και 9.55 pg/ml ± 6.5 vs 0.42 pg/ml ± 0.35 [p<.02] αντίστοιχα).Συμπέρασμα:Με βάση τα αποτελέσματα προτείνουμε πως η αγγειοπλαστική της νεφρικής αρτηρίας με τοποθέτηση stent προκαλεί μια φλεγμονώδη αντίδραση στο τοίχωμα της αρτηρίας, όπως αυτή εκφράζεται με την υψηλή συγκέντρωση ΙL-6 στο αίμα 24 ώρες μετά την επέμβαση. Όσον αφορά στην ανάπτυξη ή όχι επαναστένωσης του αγγείου προτείνουμε πως η ΙL-6 μπορεί να να αναγνωρίσει τους ασθενείς υψηλού κινδύνου και κατ’ επέκταση να αποτελέσει έναν δείκτη πρόβλεψης της επαναστένωσης.

Molecular Mechanisms of Curcumin in Neuroinflammatory Disorders: A Mini Review of Current Evidences

2019 ◽  
Vol 19 (3) ◽  
pp. 247-258 ◽  
Author(s):  
Mahsa Hatami ◽  
Mina Abdolahi ◽  
Neda Soveyd ◽  
Mahmoud Djalali ◽  
Mansoureh Togha ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
English Language ◽  
Molecular Mechanisms ◽  
Randomized Clinical Trials ◽  
Mitochondrial Dynamics ◽  
Nuclear Factor Κb ◽  
General Term ◽  
Neuroinflammatory Disease ◽  
Tnf Α ◽  
Factor Α

Objective: Neuroinflammatory disease is a general term used to denote the progressive loss of neuronal function or structure. Many neuroinflammatory diseases, including Alzheimer’s, Parkinson’s, and multiple sclerosis (MS), occur due to neuroinflammation. Neuroinflammation increases nuclear factor-κB (NF-κB) levels, cyclooxygenase-2 enzymes and inducible nitric oxide synthase, resulting in the release of inflammatory cytokines, such as interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α). It could also lead to cellular deterioration and symptoms of neuroinflammatory diseases. Recent studies have suggested that curcumin (the active ingredient in turmeric) could alleviate the process of neuroinflammatory disease. Thus, the present mini-review was conducted to summarize studies regarding cellular and molecular targets of curcumin relevant to neuroinflammatory disorders. Methods: A literature search strategy was conducted for all English-language literature. Studies that assessed the various properties of curcuminoids in respect of neuroinflammatory disorders were included in this review. Results: The studies have suggested that curcuminoids have significant anti- neuroinflammatory, antioxidant and neuroprotective properties that could attenuate the development and symptom of neuroinflammatory disorders. Curcumin can alleviate neurodegeneration and neuroinflammation through multiple mechanisms, by reducing inflammatory mediators (such as TNF-α, IL-1β, nitric oxide and NF-κB gene expression), and affect mitochondrial dynamics and even epigenetic changes. Conclusion: It is a promising subject of study in the prevention and management of the neuroinflammatory disease. However, controlled, randomized clinical trials are needed to fully evaluate its clinical potential.

A direct requirement of nuclear factor-κB for suppression of apoptosis in ventricular myocytes

2000 ◽  
Vol 279 (3) ◽  
pp. H939-H945 ◽  
Author(s):  
Shareef Mustapha ◽  
Alla Kirshner ◽  
Danielle De Moissac ◽  
Lorrie A. Kirshenbaum
Keyword(s):  
Dna Binding ◽  
Gene Transcription ◽  
Ventricular Myocytes ◽  
Vital Staining ◽  
Fold Increase ◽  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
Cytoplasmic Factor ◽  
Tnf Α ◽  
Factor Α

Nuclear factor-κB (NF-κB) is a ubiquitously expressed cellular factor regulated by the cytoplasmic factor inhibitor protein κBα (IκBα). Activation of NF-κB by cytokines, including tumor necrosis factor-α (TNF-α), requires the phosphorylation and degradation of IκBα. An anti-apoptotic role for NF-κB has recently been suggested. In the present study, we ascertained whether death-promoting signals and apoptosis mediated by TNF-α are suppressed by NF-κB in postnatal ventricular myocytes. Stimulation of myocytes with TNF-α resulted in a 12.1-fold increase ( P < 0.01) in NF-κB-dependent gene transcription and DNA binding compared with controls. This was accompanied by a corresponding increase in the NF-κB target protein A20 as determined by Western blot analysis. Vital staining revealed that TNF-α was not cytotoxic to myocytes and did not provoke apoptosis. Adenovirus-mediated delivery of a nonphosphorylatable form of IκBα to inactivate NF-κB prevented TNF-α-stimulated NF-κB-dependent gene transcription and nuclear NF-κB DNA binding. Importantly, myocytes stimulated with TNF-α and defective for NF-κB activation resulted in a 2.2-fold increase ( P < 0.001) in apoptosis. To our knowledge, the data provide the first indication that a functional NF-κB signaling pathway is crucial for suppressing death-promoting signals mediated by TNF-α in ventricular myocytes.

Localized pancreatic NF-κB activation and inflammatory response in taurocholate-induced pancreatitis

2001 ◽  
Vol 280 (6) ◽  
pp. G1197-G1208 ◽  
Author(s):  
Eva Vaquero ◽  
Ilya Gukovsky ◽  
Vjekoslav Zaninovic ◽  
Anna S. Gukovskaya ◽  
Stephen J. Pandol
Keyword(s):  
Transcription Factor ◽  
Inflammatory Response ◽  
Pancreatic Head ◽  
Pancreatic Injury ◽  
Nuclear Factor Κb ◽  
Saline Infusion ◽  
Activator Protein 1 ◽  
Local Inflammatory Response ◽  
Monocyte Chemoattractant Protein 1 ◽  
Factor Α

Transcription factor nuclear factor-κB (NF-κB) is activated in cerulein pancreatitis and mediates cytokine expression. The role of transcription factor activation in other models of pancreatitis has not been established. Here we report upregulation of NF-κB and inflammatory molecules, and their correlation with local pancreatic injury, in a model of severe pancreatitis. Rats received intraductal infusion of taurocholate or saline, and the pancreatic head and tail were analyzed separately. NF-κB and activator protein-1 (AP-1) activation were assessed by gel shift assay, and mRNA expression of interleukin-6, tumor necrosis factor-α, KC, monocyte chemoattractant protein-1, and inducible nitric oxide synthase was assessed by semiquantitative RT-PCR. Morphological damage and trypsin activation were much greater in the pancreatic head than tail, in parallel with a stronger activation of NF-κB and cytokine mRNA. Saline infusion mildly affected these parameters. AP-1 was strongly activated in both pancreatic segments after either taurocholate or saline infusion. NF-κB inhibition with N-acetylcysteine ameliorated the local inflammatory response. Correlation between localized NF-κB activation, cytokine upregulation, and tissue damage suggests a key role for NF-κB in the development of the inflammatory response of acute pancreatitis.

Increased cytochrome P-450 2E1 expression sensitizes hepatocytes to c-Jun-mediated cell death from TNF-α

2002 ◽  
Vol 282 (2) ◽  
pp. G257-G266 ◽  
Author(s):  
Hailing Liu ◽  
Brett E. Jones ◽  
Cynthia Bradham ◽  
Mark J. Czaja
Keyword(s):  
Cell Death ◽  
Oxidant Stress ◽  
Nuclear Factor Κb ◽  
Dominant Negative ◽  
Tnf Α ◽  
Cyp2e1 Expression ◽  
Factor Α ◽  
Jnk Activation ◽  
Cytochrome P 450 ◽  
Necrosis Factor

The mechanisms underlying hepatocyte sensitization to tumor necrosis factor-α (TNF-α)-mediated cell death remain unclear. Increases in hepatocellular oxidant stress such as those that occur with hepatic overexpression of cytochrome P-450 2E1 (CYP2E1) may promote TNF-α death. TNF-α treatment of hepatocyte cell lines with differential CYP2E1 expression demonstrated that overexpression of CYP2E1 converted the hepatocyte TNF-α response from proliferation to apoptotic and necrotic cell death. Death occurred despite the presence of increased levels of nuclear factor-κB transcriptional activity and was associated with increased lipid peroxidation and GSH depletion. CYP2E1-overexpressing hepatocytes had increased basal and TNF-α-induced levels of c-Jun NH2-terminal kinase (JNK) activity, as well as prolonged JNK activation after TNF-α stimulation. Sensitization to TNF-α-induced cell death by CYP2E1 overexpression was inhibited by antioxidants or adenoviral expression of a dominant-negative c-Jun. Increased CYP2E1 expression sensitized hepatocytes to TNF-α toxicity mediated by c-Jun and overwhelming oxidative stress. The chronic increase in intracellular oxidant stress created by CYP2E1 overexpression may serve as a mechanism by which hepatocytes are sensitized to TNF-α toxicity in liver disease.

The Role of Oxidative Stress, Inflammation, and Advanced Glycation End Product in Skin Manifestations of Diabetes Mellitus

2021 ◽  
Vol 17 ◽  
Author(s):  
Lili Legiawati
Keyword(s):  
Oxidative Stress ◽  
Diabetes Mellitus ◽  
Adhesion Molecule ◽  
Intercellular Adhesion Molecule ◽  
Skin Disorders ◽  
Intercellular Adhesion Molecule 1 ◽  
Tnf Α ◽  
Mitogen Activated Protein ◽  
High Level ◽  
Factor Α

: Diabetes mellitus is a metabolic disorder caused by an increase in insulin resistance, a decrease in insulin production, or both of them, resulting in a high level of blood glucose or hyperglycemia. An uncontrolled state of DM may cause complications, namely skin disorder. One or more skin disorders are found amongst 74% of T2DM patients, with the highest percentage is dry skin (47%), followed by infection (10%), diabetic hand (5%), hair loss and diabetic dermopathy (each 4%). In DM, the state of hyperglycemia and production of advanced glycaemic end-products (AGEs) profoundly impact skin changes. In the pathological pathway, AGEs induce oxidative stress and inflammation. Nonetheless, AGEs level is higher in T2DM patients compared to non-T2DM people. This is caused by hyperglycemia and oxidative stress. Binding between AGEs and receptor of AGEs (RAGE) promotes pathway of oxidative stress and inflammation cascade via mitogen-activated protein kinases (MAPK), nuclear factor-k-light-chain-enhancer of activated β cells (NF-kβ), interleukin- 6 (IL-6), tumor necrosis factor-α (TNF-α), expression of intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 2 (VCAM-2) pathway which furtherly effectuates DM complication including skin disorders.

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