scholarly journals UL16-Binding Protein 1 Induced HTR-8/SVneo Autophagy via NF-κB Suppression Mediated by TNF-α Secreted through uNK Cells

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Jing Liu ◽  
Guang Song ◽  
Tao Meng ◽  
Ge Zhao
Keyword(s):  
Nuclear Factor Kappa B ◽  
Binding Protein ◽  
Neutralizing Antibody ◽  
Trophoblast Invasion ◽  
Nuclear Factor ◽  
Inhibition Effect ◽  
Unk Cells ◽  
Tnf Α ◽  
Autophagic Activity ◽  
Dose Dependent

UL16-binding protein 1(ULBP1) has been reported to inhibit trophoblast invasion through the modification of secretion functions of uNK cells in the previous study, but its mechanisms remain unclear. In this study, we investigated the related mechanism by which upregulated ULBP1 expression impaired trophoblast invasion. We found that conditioned media with ULBP1 increased autophagy in HTR-8/SVneo, and anti-TNF-α-neutralizing antibody rescued the autophagy caused by the conditioned medium. We further found TNF-α induced autophagy in trophoblast cells in a dose-dependent way and accompanied by a decreased activity of nuclear factor-kappa B (NF-κB). Inhibition of NF-κB activation by chemical inhibitor augmented these autophagic responses to TNF-α in the cells. In addition, interruption NF-κB caused a significant decrease in HTR-8/SVneo invasion and enhanced the inhibition effect of TNF-α on HTR-8/SVneo invasion. Taken together, these findings suggest that TNF-α is able to regulate autophagic activity via suppressing NF-κB, which might be the mechanism related to ULBP1 in preeclampsia pathogenesis.

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.

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 CTRP9 protects against MIA-induced inflammation and knee cartilage damage by deactivating the MAPK/NF-κB pathway in rats with osteoarthritis

2020 ◽  
Vol 15 (1) ◽  
pp. 971-980
Author(s):  
Shicheng Zheng ◽  
Jing Ren ◽  
Sihai Gong ◽  
Feng Qiao ◽  
Jinlong He
Keyword(s):  
Synovial Fluid ◽  
Nuclear Factor Kappa B ◽  
Cartilage Damage ◽  
Cartilage Tissue ◽  
Enzyme Linked Immunosorbent Assay ◽  
Nuclear Factor ◽  
Knee Cartilage ◽  
Monosodium Iodoacetate ◽  
Dose Dependent ◽  
Different Doses

AbstractC1q/TNF-related protein 9 (CTRP9), the closest paralog of adiponectin, has been reported to protect against inflammation-related diseases. However, its role in regulating osteoarthritis (OA) has not been fully elucidated. First, a rat model of OA was generated. Furthermore, rats with OA were injected with different doses of recombinant CTRP9 protein (rCTRP9), and the knee cartilage damage was evaluated. Finally, the phosphorylation of p38 and the secretion of matrix metalloproteinases (MMPs) were detected by Western blotting and enzyme-linked immunosorbent assay. Results revealed that CTRP9 was highly expressed in adipose tissue, followed by skeletal muscle and cartilage tissue, and less expressed in liver, kidney and lung. Moreover, the expression of CTRP9 significantly decreased in the monosodium iodoacetate (MIA) group in the knee cartilage and knee synovial fluid, and the contents of interleukin-1β (IL-1β) and IL-6 significantly increased in knee synovial fluid. In addition, rCTRP9 alleviated MIA-induced inflammation, oxidative stress and knee cartilage damage in a dose-dependent way. In addition, rCTRP9 could attenuate the expression of p38MAPK and p-p38 and suppress the expression of nuclear factor-kappa B (NF-κB), p65 and MMPs. Collectively, the results of the present study suggested that CTRP9 alleviates the inflammation of MIA-induced OA through deactivating p38MAPK and NF-κB signaling pathways in rats.

scholarly journals Therapeutic effect and mechanism of action of quercetin in a rat model of osteoarthritis

2019 ◽  
Vol 48 (3) ◽  
pp. 030006051987346 ◽  
Author(s):  
Jun Zhang ◽  
Jing Yin ◽  
Daohong Zhao ◽  
Chaoran Wang ◽  
Yuhao Zhang ◽  
...  
Keyword(s):  
Therapeutic Effect ◽  
Mechanism Of Action ◽  
Rat Model ◽  
Dependent Manner ◽  
Nuclear Factor ◽  
Toll Like Receptor ◽  
Tnf Α ◽  
Dose Dependent ◽  
Light Chain Enhancer ◽  
Necrosis Factor

Objective To study the therapeutic effect and mechanism of action of quercetin in a rat model of osteoarthritis (OA). Methods The OA rat model was established by intra-articular injection of papain. Changes in knee diameter, toe volume and histopathology were measured. Levels of interleukin (IL)-β and tumor necrosis factor (TNF)-α were assessed by ELISA. Relative expression of Toll-like receptor (TLR)-4 and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) was evaluated by western blotting. Results Compared with rats treated with papain alone, changes in knee diameter, toe volume and Makin' s score were less apparent in OA rats treated with quercetin. Levels of serum IL-1β and TNF-α were also reduced in quercetin-treated OA rats. Expression of TLR-4 and NF-κB was significantly suppressed in a dose-dependent manner in quercetin-treated OA rats. Conclusion Quercetin exhibited a therapeutic effect in OA rats, which may be related to inhibition of IL-1β and TNF-α production via the TLR-4/NF-κB pathway.

Effect of Alendronate Treatment on Salivary Levels of Osteoprotegrin and TNF-α in Postmenopausal Woman with Osteoporosis and Periodontal Diseases

2018 ◽  
Vol 30 (2) ◽  
pp. 17-22
Author(s):  
Aseel J. Ibraheem ◽  
Aysar N. Mohammed
Keyword(s):  
Bone Resorption ◽  
Postmenopausal Women ◽  
Nuclear Factor Kappa B ◽  
Periodontal Diseases ◽  
Control Group ◽  
Nuclear Factor ◽  
Decoy Receptor ◽  
Tnf Α ◽  
Receptor Activator ◽  
Alendronate Treatment

Background: All diseases concerning bone destruction such as osteoporosis and periodontal diseases share common pattern in which the osteoclast cells are absolutely responsible for bone resorption that occurred when osteoclast activity exceeds osteoblast activity. Osteoprotegrin (OPG) considered as novel soluble decoy receptor known as “bone protector” since it prevents extreme bone resorption through inhibition of differentiation and activity of osteoclast by competing for binding site. It binds to receptor activator of nuclear factor kappa-B ligand (RANKL) and prevent its interaction with receptor activator of nuclear factor kappa-B (RANK), thus inhibits osteoclast formation. TNF-α is a pro-inflammatory cytokines having a broad range of important roles in regulation of immune system and bone resorption through the stimulation of osteoclastogenesis. Alendronate (ALN) diminishes the expression of osteoclast activating factors and cytokines such as RANKL and enhances the production of decoy receptor osteoprotegerin in osteoblast cells. Moreover, it decreases the production of proinflammatory cytokines such as TNF-α by macrophage, stimulates apoptosis of monocyte-macrophage cell lines derivative and reduces inflammatory response. Aims of the Study: 1. To assess the effect of alendronate treatment on salivary levels of osteoprotegrin and TNF-α in postmenopausal women with osteoporosis and periodontal disease 2. To find any possible correlation between salivary levels of osteoprotegrin and TNF-α in control and study groups. Materials and Methods: Total sample of 90 female subjects (55-65 years) were divided into 3 groups, (30 subjects in each group): first control group involved systemically healthy subjects with healthy periodontium, second group involved postmenopausal women with osteoporosis under alendronate treatment for(3-6)months (alendronate group), third group involved postmenopausal women with osteoporosis without alendronate treatment(osteoporosis group). The last two groups were sub- divided in- to two sub –groups (15 subjects in each sub-group) of gingivitis and periodontitis subjects respectively. Salivary samples were collected from all subjects and salivary levels of osteoprotegrin and TNF- α were determined by enzyme –linked immune sorbent assay (ELISA). Results: Highest median value of salivary (OPG) was found in alendronate group followed by control group while the lowest value was found in osteoporosis group. Highest median value of TNF- α was found in osteoporosis group followed by control group and alendronate group respectively with highly significant differences between them. Spearman correlation between salivary levels of TNF-α and OPG showed non- significant correlation at all subgroups. Conclusion: Subjects with osteoporosis in this study had greater levels of TNF-α and decrease in the level of OPG comparing with patients under alendronate treatment. Alendronate treatment for women with osteoporosis and periodontal disease may have beneficial outcome.

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.

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