Inhibition of TNF-α stimulated nuclear factor-kappa B (NF-κB) activation by cyclometalated platinum(ii) complexes

2012 ◽  
Vol 48 (2) ◽  
pp. 230-232 ◽  
Author(s):  
Jia Liu ◽  
Raymond Wai-Yin Sun ◽  
Chung-Hang Leung ◽  
Chun-Nam Lok ◽  
Chi-Ming Che
Keyword(s):  
Nuclear Factor Kappa B ◽  
Nuclear Factor ◽  
Nuclear Factor Kappa ◽  
Tnf Α

scholarly journals The Effect of Neddylation Inhibition on Inflammation-Induced MMP9 Gene Expression in Esophageal Squamous Cell Carcinoma

2021 ◽  
Vol 22 (4) ◽  
pp. 1716
Author(s):  
Anita Hryniewicz-Jankowska ◽  
Jaroslaw Wierzbicki ◽  
Renata Tabola ◽  
Kamilla Stach ◽  
Khalid Sossey-Alaoui ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Migration ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Nuclear Factor Kappa B ◽  
Nuclear Factor ◽  
Nuclear Factor Kappa ◽  
Tnf Α ◽  
Mmp9 Gene

Inhibition of the protein neddylation process by the small-molecule inhibitor MLN4924 has been recently indicated as a promising direction for cancer treatment. However, the knowledge of all biological consequences of MLN4924 for cancer cells is still incomplete. Here, we report that MLN4924 inhibits tumor necrosis factor-alpha (TNF-α)-induced matrix metalloproteinase 9 (MMP9)-driven cell migration. Using real-time polymerase chain reaction (PCR) and gelatin zymography, we found that MLN4924 inhibited expression and activity of MMP9 at the messenger RNA (mRNA) and protein levels in both resting cells and cells stimulated with TNF-α, and this inhibition was closely related to impaired cell migration. We also revealed that MLN4924, similar to TNF-α, induced phosphorylation of inhibitor of nuclear factor kappa B-alpha (IκB-α). However, contrary to TNF-α, MLN4924 did not induce IκB-α degradation in treated cells. In coimmunoprecipitation experiments, nuclear IκB-α which formed complexes with nuclear factor kappa B p65 subunit (NFκB/p65) was found to be highly phosphorylated at Ser32 in the cells treated with MLN4924, but not in the cells treated with TNF-α alone. Moreover, in the presence of MLN4924, nuclear NFκB/p65 complexes were found to be enriched in c-Jun and cyclin dependent kinase inhibitor 1 A (CDKN1A/p21) proteins. In these cells, NFκB/p65 was unable to bind to the MMP9 gene promoter, which was confirmed by the chromatin immunoprecipitation (ChIP) assay. Taken together, our findings identified MLN4924 as a suppressor of TNF-α-induced MMP9-driven cell migration in esophageal squamous cell carcinoma (ESCC), likely acting by affecting the nuclear ubiquitin–proteasome system that governs NFκB/p65 complex formation and its DNA binding activity in regard to the MMP9 promoter, suggesting that inhibition of neddylation might be a new therapeutic strategy to prevent invasion/metastasis in ESCC patients.

scholarly journals Circulating Nuclear Factor-Kappa B Mediates Cancer-Associated Inflammation in Human Breast and Colon Cancer

2020 ◽  
Author(s):  
Hafize Uzun ◽  
Berrin Papila Kundaktepe ◽  
Volkan Sozer ◽  
Pinar Kocael ◽  
Sinem Durmus ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Colon Cancer ◽  
Nuclear Factor Kappa B ◽  
Enzyme Linked Immunosorbent Assay ◽  
Nuclear Factor ◽  
Healthy Controls ◽  
Nuclear Factor Kappa ◽  
Tnf Α ◽  
Study Results ◽  
Serum Crp

Background: Inflammation is recognized as a hallmark feature of cancer development and progression. The aim of our study was to investigate the significance of serum nuclear factor kappa-B (NF-кB) levels as a circulating marker in the monitor of inflammation in breast and colon cancer; to show the relationship between NF-кB with inflammatory parameters as tumor necros faktor-α (TNF-α), soluble TNF-related apoptosis inducing ligand (sTRAIL), interleukin-6 (IL-6), pentraxin-3 (PTX-3), procalcitonin (PCT), and C-reactive protein (CRP) levels. Methods: Serum NF-кB, TNF-α, sTRAIL, IL-6, PTX-3, PCT, and serum CRP levels were measured using enzyme linked immunosorbent assay (ELISA) in 40 patients with breast cancer, 40 patients with colon cancer and 30 healthy controls. Results: The serum NF-кB, TNF-α, IL-6, PTX-3, PCT and serum CRP concentration was significantly higher and the serum sTRAIL concentration was significantly lower in patients with breast and colon cancer than in those with an healthy controls. NF-кB were positive correlated with CRP and negative corelated with sTRAIL. Conclusions: These results suggest that increased NF-кB may decrease the clinical efficacy of sTRAIL in solid tumour cells. There is relationship between inflammation and carcinogenesis so that the development of cancer occurs with chronic inflammation in breast and colon. The study results have shown that colon and breast cancer patients have increased systemic inflammation, as measured by increased circulating cytokines, and acute phase proteins, or by abnormalities in circulating cells. NF-кB may combine with other markers of the systemic inflammatory response in prognostic scores in cancer. In addition to surgical resection of the tumor, conventional radio- and chemotherapy for cancer treatment, the use of sTRAIL or other agonists for cancer therapy appeared a new potential therapy.  

scholarly journals A20 of nucleus pulposus cells plays a self-protection role via the nuclear factor-kappa B pathway in the inflammatory microenvironment

2020 ◽  
Vol 9 (5) ◽  
pp. 225-235
Author(s):  
Xin Peng ◽  
Cong Zhang ◽  
Jun-Ping Bao ◽  
Lei Zhu ◽  
Rui Shi ◽  
...  
Keyword(s):  
Nucleus Pulposus ◽  
Messenger Rna ◽  
Nuclear Factor Kappa B ◽  
Intervertebral Discs ◽  
Control Group ◽  
Nuclear Factor ◽  
Nucleus Pulposus Cells ◽  
Necrosis Factor Alpha ◽  
Nuclear Factor Kappa ◽  
Tnf Α

Aims Inflammatory response plays a pivotal role in the pathophysiological process of intervertebral disc degeneration (IDD). A20 (also known as tumour necrosis factor alpha-induced protein 3 (TNFAIP3)) is a ubiquitin-editing enzyme that restricts nuclear factor-kappa B (NF-κB) signalling. A20 prevents the occurrence of multiple inflammatory diseases. However, the role of A20 in the initiation of IDD has not been elucidated. The aim of the study was to investigate the effect of A20 in senescence of TNF alpha (TNF-α)-induced nucleus pulposus cells (NPCs). Methods Immunohistochemical staining was performed to observe the expression of A20 in normal and degenerated human intervertebral discs. The NPCs were dissected from the tail vertebrae of healthy male Sprague-Dawley rats and were cultured in the incubator. In the experiment, TNF-α was used to mimic the inflammatory environment of IDD. The cell viability and senescence were examined to investigate the effect of A20 on TNF-α-treated NPCs. The expression of messenger RNA (mRNA)-encoding proteins related to matrix macromolecules (collagen II, aggrecan) and senescence markers (p53, p16). Additionally, NF-κB/p65 activity of NPCs was detected within different test compounds. Results The expression of A20 was upregulated in degenerate human intervertebral discs. The A20 levels of NPCs in TNF-α inflammatory microenvironments were dramatically higher than those of the control group. TNF-α significantly decreased cell proliferation potency but increased senescence-associated beta-galactosidase (SA-β-Gal) activity, the expression of senescence-associated proteins, the synthesis of extracellular matrix, and G1 cycle arrest. The senescence indicators and NF-κB/p65 expression of A20 downregulated group treated with TNF-α were significantly upregulated compared to TNF-α-treated normal NPCs. Conclusion A20 has a self-protective effect on the senescence of NPCs induced by TNF-α. The downregulation of A20 in NPCs exacerbated the senescence of NPCs induced by TNF-α. Cite this article: Bone Joint Res. 2020;9(5):225–235.

The soy isoflavone genistein blunts nuclear factor kappa-B, MAPKs and TNF-α activation and ameliorates muscle function and morphology in mdx mice

2011 ◽  
Vol 21 (8) ◽  
pp. 579-589 ◽  
Author(s):  
Sonia Messina ◽  
Alessandra Bitto ◽  
M’hammed Aguennouz ◽  
Gian Luca Vita ◽  
Francesca Polito ◽  
...  
Keyword(s):  
Muscle Function ◽  
Nuclear Factor Kappa B ◽  
Mdx Mice ◽  
Nuclear Factor ◽  
Soy Isoflavone ◽  
Nuclear Factor Kappa ◽  
Tnf Α

Reduced inflammatory and phagocytotic responses following normobaric hypoxia exercise despite evidence supporting greater immune challenge

2020 ◽  
Vol 45 (6) ◽  
pp. 628-640
Author(s):  
Garrett W. Hill ◽  
Trevor L. Gillum ◽  
Ben J. Lee ◽  
Phebe A. Romano ◽  
Zach J. Schall ◽  
...  
Keyword(s):  
Nuclear Factor Kappa B ◽  
Treadmill Exercise ◽  
Normobaric Hypoxia ◽  
Repeated Measure ◽  
Intercellular Adhesion Molecule ◽  
Nuclear Factor ◽  
Fatty Acid Binding ◽  
Nuclear Factor Kappa ◽  
Inflammatory Status ◽  
Tnf Α

This study examined changes in immune markers following sustained treadmill exercise in normobaric hypoxia. Ten subjects performed 1 h of treadmill exercise (65% maximal oxygen uptake) under normoxic (NORM: fraction of inspired oxygen (FIO2) = 20.9%) and normobaric hypoxic (HYP: FIO2 = 13.5%) conditions. Blood samples, collected before, after (Post), 1 h after (1-Post), and 4 h after (4-Post) exercise, were assayed for plasma cytokines (interleukin (IL)-1RA/IL-1β/IL-8/tumor necrosis factor alpha (TNF-α)) and markers of leukocyte activation (macrophage inflammatory protein-1β (MIP-1β)/myeloperoxidase (MPO)/soluble intercellular adhesion molecule-1 (sICAM-1)) using ELISA. Pro- to anti-inflammatory cytokine ratios (TNF-α/IL-1RA; IL-1β/IL-1RA) were calculated. Peripheral blood mononuclear cells (PBMC) were analyzed for changes in inflammatory status (phosphorylated nuclear factor kappa B/nuclear factor kappa B) using Western Blot. Data were analyzed with 2-way (condition × time) repeated-measure ANOVAs with Newman–Keuls post hoc tests. MIP-1β was elevated at 1-Post HYP exercise (+11%; p < 0.01) but did not increase following exercise in NORM. TNF-α/IL-1RA and IL-1β/IL-1RA ratios were both reduced (p < 0.05) following HYP exercise (−16% and −52%, respectively, at 1-Post and −7% and −32%, respectively, at 4-Post). IL-8 increased (p < 0.05) at Post and 1-Post NORM (+33% and +57%, respectively) and HYP (+60% and +83%, respectively) exercise, but was not different between conditions (p > 0.05). Interestingly, plasma sICAM-1 did not increase (p > 0.05) following NORM exercise but was increased (p < 0.05) at Post (+17%), 1-Post (+16%), and 4-Post (+14%) HYP exercise. There was also a delayed peak in plasma MPO concentrations following HYP exercise and PBMC exhibited a reduced (p < 0.05) inflammatory capacity at Post (−38%) and 1-Post (−49%). Novelty Following HYP exercise, participants exhibited (i) circulatory bias towards anti-inflammation; (ii) elevated sICAM; (iii) delayed peak in plasma MPO; and (iv) diminished inflammatory response in PBMC. Collectively, these data suggest immunosuppression. This is undesirable, given that elevated MIP-1β (reported here) and elevated intestinal fatty acid binding protein (reported previously) both suggest higher lipopolysaccharide concentrations following HYP exercise.

scholarly journals TNF-α enhances estrogen-induced cell proliferation of estrogen-dependent breast tumor cells through a complex containing nuclear factor-kappa B

Oncogene ◽  
2005 ◽  
Vol 25 (9) ◽  
pp. 1367-1377 ◽  
Author(s):  
M F Rubio ◽  
S Werbajh ◽  
E G A Cafferata ◽  
A Quaglino ◽  
G P Coló ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Tumor Cells ◽  
Breast Tumor ◽  
Nuclear Factor Kappa B ◽  
Nuclear Factor ◽  
Breast Tumor Cells ◽  
Nuclear Factor Kappa ◽  
Tnf Α

Lipopolysaccharide and TNF-α Activate the Nuclear Factor Kappa B Pathway in the Human Placental JEG-3 Cells

Placenta ◽  
2006 ◽  
Vol 27 (6-7) ◽  
pp. 568-575 ◽  
Author(s):  
M. Lappas ◽  
K. Yee ◽  
M. Permezel ◽  
G.E. Rice
Keyword(s):  
Nuclear Factor Kappa B ◽  
Nuclear Factor ◽  
Nuclear Factor Kappa ◽  
Tnf Α

scholarly journals Παράγοντες που οδηγούν σε έκτοπη οστεοποίηση μετά από κρανιοεγκεφαλική κάκωση

2014 ◽  
Author(s):  
Παναγιώτα Σακελλαράκη
Keyword(s):  
Nuclear Factor Kappa B ◽  
Cytometric Bead Array ◽  
Nuclear Factor ◽  
Soluble Receptor ◽  
Procollagen Type ◽  
Amino Terminal ◽  
Nuclear Factor Kappa ◽  
Tnf Α ◽  
Receptor Activator

Με τον όρο «Έκτοπη Οστεοποίηση» περιγράφεται ο σχηματισμός οστού σε σημεία που υπό φυσιολογικές συνθήκες δεν υφίσταται. Τα σημεία αυτά μπορεί να είναι μύες, τένοντες ή σύνδεσμοι και γενικότερα μεσεγχυματικού τύπου μαλακά μόρια, κυρίως γύρω από τις μεγαλύτερες αρθρώσεις. Η επίκτητη μορφή της νόσου, που είναι και η πιο κοινή, εμφανίζεται μετά από μυοσκελετικούς τραυματισμούς, κακώσεις του νωτιαίου μυελού και του κεντρικού νευρικού συστήματος γενικότερα, αλλά και σε περιπτώσεις σοβαρών εγκαυμάτων. Η παθοφυσιολογία της έκτοπης οστεοποίησης παραμένει άγνωστη, αυτό που γνωρίζουμε με βεβαιότητα είναι ότι για τον σχηματισμό της απαιτούνται τρείς βασικές προϋποθέσεις που είναι α) τα οστεοπρογονικά κύτταρα, β) οι κατάλληλοι επαγωγικοί παράγοντες και γ) το ευνοϊκό οστεοεπαγωγικό περιβάλλον. Στην παρούσα εργασία με την χρήση κυτταρομετρίας ροής, δοκιμασιών με ηλεκτροχημειοφωταύγεια, Elisa και ανοσοπροσδιορισμού με χρήση Cytometric Bead Array προσδιορίσαμε τις συγκεντρώσεις των total procollagen type 1 amino-terminal propeptide (TP1NP), osteoprotegerin (OPG), β-isomerized C-terminal telopeptides (β- Crosslaps), soluble receptor activator of nuclear factor kappa-B ligand (sRANKL), N-MID osteocalcin, S100 και των κυτταροκινών IL-2, IL-4, IL-6, IL-10, INF-γ και TNF-a στον ορό ασθενών και υγιών μαρτύρων. Επιπλέον, στο ολικό αίμα προσδιορίσαμε τον πληθυσμό των θετικών στην οστεοκαλσίνη κυττάρων. Όλα τα προς μελέτη μόρια είχαν άμεση ή έμμεση σχέση με την οστική ανακατασκευή και τις φλεγμονώδεις αντιδράσεις. Συνολικά μελετήθηκαν 55 ασθενείς από τους οποίους ελήφθησαν δείγματα καθόλη την διάρκεια νοσηλείας τους. Οι ασθενείς μελετήθηκαν με βάση το είδος του τραύματος, την εμφάνιση ή όχι έκτοπης οστεοποίησης και την έκβαση της κατάστασης τους. Επιπλέον, οι επιμέρους ομάδες ασθενών μελετήθηκαν συναρτήσει του χρόνου.Τα αποτελέσματα μας έδειξαν ότι στο σύνολο των ασθενών παρατηρήθηκαν στατιστικά μειωμένα επίπεδα β- crosslaps, N-MID osteocalcin, sRANKL και S100 συγκριτικά με τους υγιείς μάρτυρες. Αντίθετα, τα επίπεδα των TP1NP, των θετικών στην οστεοκαλσίνη κυττάρων, της OPG, της INF-γ και της IL-6 ήταν στατιστικά σημαντικά αυξημένα. Επιπλέον, στατιστικά σημαντικά αυξημένα παρατηρήθηκαν τα επίπεδα του S100 στους ασθενείς που είχαν υποστεί κρανιοεγκεφαλικές κακώσεις κατά το πρώτο εικοσιτετράωρο μετά την επαγωγή της κάκωσης. Στατιστικά σημαντικά αυξημένο επίσης παρατηρήθηκε και στην ομάδα των ασθενών με κακή έκβαση συγκριτικά με τους υγιείς δότες. Στην ίδια ομάδα ασθενών παρατηρήθηκε μια γενικευμένη αύξηση των επιπέδων των κυτταροκινών που φαίνεται να σχετίζεται άμεσα με την κακή έκβαση της κατάστασης τους. Πιο συγκεκριμένα η αύξηση αυτή ήταν στατιστικώς σημαντική για τις IL-4, INF-γ και TNF-α.

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