scholarly journals 2441 INTERLEUKIN-1B AND CYCLOOXYGENASE-2 PROINFLAMMATION ANALYSIS AND IN SILICO DOCKING NUCLEAR FACTOR KAPPA B ON ENDOMETRIOSIS CELL CULTURE GIVEN HEPTYL GALLATE AND OCTYL GALLATE TREATMENT

2019 ◽  
pp. 503-506
Author(s):  
ARLENI BUSTAMI ◽  
FAJAR SULISTYA UTAMI ◽  
RAHMI BUDIARTI ◽  
HERI WIBOWO
Keyword(s):  
Cell Culture ◽  
Gallic Acid ◽  
In Silico ◽  
Nuclear Factor Kappa B ◽  
Enzyme Linked Immunosorbent Assay ◽  
Nuclear Factor ◽  
In Silico Docking ◽  
Nuclear Factor Kappa ◽  
Proinflammatory Factor ◽  
Cox 2

Objective: The aim of this study is to analyze the effect of octyl gallate and heptyl gallate toward the regulation of interleukin-1β and cyclooxygenase (COX)-2 proinflammatory factor on endometriosis cell culture and analyze its activity toward nuclear factor kappa B (NFkB) target protein through in silico docking technique. Methods: In vitro study was performed on endometriosis cells cultured treated with two dosages each of heptyl and octyl gallate (51.2 μg/mL and 102.4 μg/mL) for 48 h, then followed by 10 ng/mL lipopolysaccharides (LPS) induction for 24 h. The positive control group was treated by LPS induced and the negative control was treated without LPS. Inflammation regulation was evaluated with enzyme-linked immunosorbent assay technique and in silico docking analyzed using bioinformatics technique. Results: Molecular docking analysis with gallic acid and their derivatives showed that more stable affinity and stronger binding found on octyl gallate than heptyl gallate and gallic acid at the active site of NFkB. Conclusions: Based on this study results, octyl gallate and heptyl gallate were proven to be able to reduce COX-2 proinflammatory factor through NFkB pathway as an inflammatory regulator; thus, it has the potential to be developed as a therapy for endometriosis.

scholarly journals 17-Aminogeldanamycin Inhibits Constitutive Nuclear Factor-Kappa B (NF-κB) Activity in Patient-Derived Melanoma Cell Lines

2020 ◽  
Vol 21 (11) ◽  
pp. 3749
Author(s):  
Mariusz L. Hartman ◽  
Magdalena Rogut ◽  
Aleksandra Mielczarek-Lewandowska ◽  
Michal Wozniak ◽  
Malgorzata Czyz
Keyword(s):  
Cell Lines ◽  
Melanoma Cell ◽  
Nuclear Factor Kappa B ◽  
Time Lapse ◽  
Genetic Alterations ◽  
Enzyme Linked Immunosorbent Assay ◽  
Nuclear Factor ◽  
Nuclear Factor Kappa ◽  
Promising Therapeutic Approach ◽  
Melanoma Cell Lines

Melanoma remains incurable skin cancer, and targeting heat shock protein 90 (HSP90) is a promising therapeutic approach. In this study, we investigate the effect of 17-aminogeldanamycin, a potent HSP90 inhibitor, on nuclear factor-kappa B (NF-κB) activity in BRAFV600E and NRASQ61R patient-derived melanoma cell lines. We performed time-lapse microscopy and flow cytometry to monitor changes in cell confluence and viability. The NF-κB activity was determined by immunodetection of phospho-p65 and assessment of expression of NF-κB-dependent genes by quantitative real-time polymerase chain reaction (qRT-PCR), Western blotting, and enzyme-linked immunosorbent assay (ELISA). Constitutive activity of p65/NF-κB was evident in all melanoma cell lines. Differences in its level might be associated with genetic alterations in CHUK, IL1B, MAP3K14, NFKBIE, RIPK1, and TLR4, while differences in transcript levels of NF-κB-inducible genes revealed by PCR array might result from the contribution of other regulatory mechanisms. 17-Aminogeldanamycin markedly diminished the level of phospho-p65, but the total p65 protein level was unaltered, indicating that 17-aminogeldanamycin inhibited activation of p65/NF-κB. This conclusion was supported by significantly reduced expression of selected NF-κB-dependent genes: cyclin D1 (CCND1), C-X-C motif chemokine ligand 8 (CXCL8), and vascular endothelial growth factor (VEGF), as shown at transcript and protein levels, as well as secretion of IL-8 and VEGF. Our study indicates that 17-aminogeldanamycin can be used for efficient inhibition of NF-κB activity and the simultaneous diminution of IL-8 and VEGF levels in the extracellular milieu of melanoma.

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.  

The protective role of etoricoxib against diethylnitrosamine/2-acetylaminofluorene-induced hepatocarcinogenesis in Wistar rats: The impact of NF-κB/COX-2/PGE2 signaling

2021 ◽  
Vol 14 ◽  
Author(s):  
Gaber F. Ali ◽  
Hany A. Omar ◽  
Fatema Hersi ◽  
Amira M. Abo-Youssef ◽  
Osama M. Ahmed ◽  
...  
Keyword(s):  
Liver Cancer ◽  
Wistar Rats ◽  
Nuclear Factor Kappa B ◽  
Interleukin 1 ◽  
Lipid Peroxide ◽  
Nuclear Factor ◽  
Nonalcoholic Fatty Liver ◽  
Nuclear Factor Kappa ◽  
Cox 2 ◽  
The Impact

Background: Liver cancer ranks as the 7th and 5th leading cause of cancer morbidity worldwide in men and women, respectively. Hepatocellular carcinoma (HCC) is the most common type of liver cancer and is associated with an increasing global burden of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). Objective: The present study aimed to investigate the possible chemopreventive effect of etoricoxib on diethylnitrosamine (DENA) and 2-acetylaminofluorene (2AAF)-induced HCC in male Wistar rats. Methods: HCC was induced by DENA (150 mg/kg/week; i.p) for 2 weeks, then 2AAF (20 mg/kg; p.o) every other day for three successive weeks. Etoricoxib (0.6 mg/kg, p.o.) was given to DENA/2AAF-administered rats for 20 weeks. Results: Etoricoxib significantly suppressed alpha-fetoprotein (AFP) and carbohydrate antigen 19-9 (CA19.9) as liver tumor biomarkers. It also decreased serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin levels while increasing serum albumin levels. Besides, it alleviated DENA/2AAF-induced histopathological abrasions and inflammatory cell infiltration. Furthermore, etoricoxib showed a potent antioxidant effect, supported by a significant lipid peroxide reduction and elevation in superoxide dismutase and GSH content activity. In addition, Etoricoxib significantly down-regulated the protein expression of interleukin 1 beta (IL-1β), tumor necrosis factor α (TNFα), nuclear Factor-kappa B (NF-κB), phosphorylated nuclear Factor-kappa B (p-NF-κB), cyclooxygenase-2 (COX-2), and prostaglandin E2 (PGE2). Conclusion: In conclusion, the current results proved that etoricoxib possesses an anticarcinogenic effect via its antioxidant, anti-inflammatory, and modulation of NF-κB/COX-2/PGE2 signaling.

scholarly journals KCHO-1, a Novel Antineuroinflammatory Agent, Inhibits Lipopolysaccharide-Induced Neuroinflammatory Responses through Nrf2-Mediated Heme Oxygenase-1 Expression in Mouse BV2 Microglia Cells

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Dong-Sung Lee ◽  
Wonmin Ko ◽  
Chi-Su Yoon ◽  
Dong-Cheol Kim ◽  
Jinju Yun ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Neurodegenerative Diseases ◽  
Heme Oxygenase ◽  
Nuclear Factor Kappa B ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Nuclear Factor ◽  
Nuclear Factor Kappa ◽  
Bv2 Microglia ◽  
Cox 2

The brain is vulnerable to oxidative stress and inflammation that can occur as a result of aging or neurodegenerative diseases. Our work has sought to identify natural products that regulate heme oxygenase (HO)-1 and to determine their mechanism of action in neurodegenerative diseases. KCHO-1 is a novel herbal therapeutic containing 30% ethanol (EtOH) extracts from nine plants. In this study, we investigated the antineuroinflammatory effects of KCHO-1 in lipopolysaccharide- (LPS-) treated mouse BV2 microglia. KCHO-1 inhibited the protein expression of inducible nitric oxide synthase (iNOS), iNOS-derived nitric oxide (NO), cyclooxygenase- (COX-) 2, and COX-2-derived prostaglandin E2 (PGE2) in LPS-stimulated BV2 microglia. It also reduced tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), and IL-6 production. This effect was correlated with the suppression of inhibitor of nuclear factor kappa B-α(IκB-α) phosphorylation and degradation and nuclear factor kappa B (NF-κB) translocation and DNA binding. Additionally, KCHO-1 upregulated HO-1 expression by promoting nuclear translocation of nuclear factor E2-related factor 2 (Nrf2) in mouse BV2 microglia. Tin protoporphyrin (SnPP), an HO activity inhibitor, was used to verify the inhibitory effects of KCHO-1 on proinflammatory mediators and proteins associated with HO-1 expression. Our data suggest that KCHO-1 has therapeutic potential in neurodegenerative diseases caused by neuroinflammation.

BaeR protein acts as an activator of nuclear factor-kappa B and Janus kinase 2 to induce inflammation in murine cell lines

2016 ◽  
Vol 62 (9) ◽  
pp. 753-761
Author(s):  
Seung-Jin Lee ◽  
Biruk Tesfaye Birhanu ◽  
Elias Gebru Awji ◽  
Myung Hee Kim ◽  
Ji-Yong Park ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Nuclear Factor Kappa B ◽  
Inflammatory Responses ◽  
Janus Kinase ◽  
Cytokine Gene Expression ◽  
Raw 264.7 Cells ◽  
Nuclear Factor ◽  
Janus Kinase 2 ◽  
Nuclear Factor Kappa ◽  
Cox 2

BaeR, a response regulator protein, takes part in multidrug efflux, bacterial virulence activity, and other biological functions. Recently, BaeR was shown to induce inflammatory responses by activating the mitogen-activated protein kinases (MAPKs). In this study, we investigated additional pathways used by BaeR to induce an inflammatory response. BaeR protein was purified from Salmonella enterica Paratyphi A and subcloned into a pPosKJ expression vector. RAW 264.7 cells were treated with BaeR, and RNA was extracted by TRIzol reagent for RT-PCR. Cytokine gene expression was analyzed by using the comparative cycle threshold method, while western blotting and ELISA were used to assess protein expression. We confirmed that BaeR activates nuclear factor-kappa B (NF-κB), thereby inducing an inflammatory response and increases the production of interleukins (IL-)1β and IL-6. During this process, the Janus kinase 2 (JAK2)–STAT1 signaling pathway was activated, resulting in an increase in the release of interferons I and II. Additionally, COX-2 was activated and its expression increased with time. In conclusion, BaeR induced an inflammatory response through activation of NF-κB in addition to the MAPKs. Furthermore, activation of the JAK2–STAT1 pathway and COX-2 facilitated the cytokine binding activity, suggesting an additional role for BaeR in the modulation of the immune system of the host and the virulence activity of the pathogen.

scholarly journals The Relationship between Serum and Gene Expression Levels of RANK, RANKL and Osteoprotegerin Inflammatory Pathway with Unstable Angina: A Case-control Study

2021 ◽  
Author(s):  
Alireza Farrokhian ◽  
Mahtab Miraftab ◽  
Minoo Chenari ◽  
Hossein Akbari ◽  
Hassan Nikoueinejad ◽  
...  
Keyword(s):  
Gene Expression ◽  
Unstable Angina ◽  
Nuclear Factor Kappa B ◽  
Mononuclear Cells ◽  
Serum Levels ◽  
Enzyme Linked Immunosorbent Assay ◽  
Nuclear Factor ◽  
Inflammatory Pathway ◽  
Nuclear Factor Kappa ◽  
Receptor Activator

Osteoprotegerin (OPG), receptor activator of nuclear factor-kappa B (RANK) and receptor activator of nuclear factor-kappa B ligand (RANKL), the members of the tumor necrosis factor (TNF) family, have multiple effects on bone metabolism, endocrine functions and, as an inflammatory pathway, in the immune system. This study tried to determine the association of the OPG/RANKL/RANK axis with the severity of unstable angina (UA) as an inflammatory condition. Our study involved 50 patients with UA and 50 healthy people. Serum and peripheral blood mononuclear cells were isolated from all participants. Serum levels and gene expression of OPG, RANKL, and RANK in mononuclear cells were measured by enzyme-linked immunosorbent assay (ELISA) and real-time polymerase chain reaction (RT-PCR), respectively. For each patient with UA, the thrombolysis in myocardial infarction (TIMI) and the global registry of acute coronary events (GRACE) scores were determined to evaluate the severity of the disease. Then we analyzed the relation of OPG, RANKL, and RANK levels with TIMI and GRACE scores in patients with UA. Discriminate analysis was used to predict the combinational models of such factors on the prediction of UA. Serum levels of OPG and RANKL (p<0.001) and gene expression of RANKL (p<0.001) were significantly more in patients than those in healthy ones. No relation was seen between the OPG/RANKL/RANK axis and the severity of UA according to TIMI and GRACE scores. Our study shows that serum level, as well as gene expression of OPG/RANKL/RANK axis neither, predicts the occurrence of UA nor shows any relationship with its severity.  

scholarly journals Pharmacological Targets of Kaempferol Within Inflammatory Pathways—A Hint Towards the Central Role of Tryptophan Metabolism

Antioxidants ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 180 ◽  
Author(s):  
Stefanie Hofer ◽  
Simon Geisler ◽  
Rebecca Lisandrelli ◽  
Hieu Nguyen Ngoc ◽  
Markus Ganzera ◽  
...  
Keyword(s):  
Nuclear Factor Kappa B ◽  
Mononuclear Cells ◽  
Catalytic Domain ◽  
Human Peripheral Blood ◽  
Immunomodulatory Activity ◽  
Nuclear Factor ◽  
Peripheral Blood Mononuclear ◽  
In Silico Docking ◽  
Nuclear Factor Kappa

The flavonoid kaempferol is almost ubiquitously contained in edible and medicinal plants and exerts a broad range of interesting pharmacological activities. Interactions with central inflammatory processes can be exploited to treat or attenuate symptoms of disorders associated with chronic immune activation during infections, malignancies, and neurodegenerative or cardiovascular disorders. Many drugs, phytochemicals, and nutritional components target the catabolism of the essential amino acid tryptophan by indoleamine 2,3-dioxygenase 1 (IDO-1) for immunomodulation. We studied the effects of kaempferol by in vitro models with human peripheral blood mononuclear cells (PBMC) and THP-1 derived human myelomonocytic cell lines. Kaempferol suppressed interferon-γ dependent immunometabolic pathways: Formation of the oxidative stress biomarker neopterin and catabolism of tryptophan were inhibited dose-dependently in stimulated cells. In-silico docking studies revealed a potential interaction of kaempferol with the catalytic domain of IDO-1. Kaempferol stimulated nuclear factor kappa B (NF-κB) signaling in lipopolysaccharide (LPS)-treated THP-1 cells, thereby increasing the mRNA expression of interleukin (IL) 1 beta, tumor necrosis factor, and nuclear factor kappa B subunit 1, while IL6 was downregulated. Data suggest that concerted effects of kaempferol on multiple immunologically relevant targets are responsible for its immunomodulatory activity. However, the immunosuppressive effects may be more relevant in a T-cell dominated context.

scholarly journals The Long Noncoding RNA ANRIL Promotes Cell Apoptosis in Lipopolysaccharide-Induced Acute Kidney Injury Mediated by the TLR4/Nuclear Factor-Kappa B Pathway

2020 ◽  
Vol 45 (2) ◽  
pp. 209-221 ◽  
Author(s):  
Ye Zhu ◽  
Sheng-Wei Wei ◽  
Ao Ding ◽  
Wei-Ping Zhu ◽  
Mei-Fang Mai ◽  
...  
Keyword(s):  
Noncoding Rna ◽  
Nuclear Factor Kappa B ◽  
Quantitative Polymerase Chain Reaction ◽  
Kidney Tissue ◽  
Inflammatory Factors ◽  
Luciferase Reporter ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Nuclear Factor ◽  
Nuclear Factor Kappa

Background/Aims: The purpose of this study is to analyze the expression and biological function of lncRNA ANRIL, microRNA-199a, TLR4, and nuclear factor-kappa B (NF-κB) in acute renal injury (AKI) induced by lipopolysaccharide (LPS). Methods: The levels of ANRIL and microRNA-199a in mouse cells and kidneys were detected by quantitative-polymerase chain reaction. Western blot analysis was used for the NF-κB pathway protein. MTT assay was used for cell viability. Enzyme-linked immunosorbent assay was used for the secretion of inflammatory factors in mouse kidney tissue. Apoptosis was measured by flow cytometry and Western blotting. The potential binding region between ANRIL and miR-199a was verified by luciferase reporter assay. Results: The upregulation of ANRIL can reduce the expression of microRNA-199a and increases the number of apoptotic cells. The expression levels of ANRIL in LPS-induced AKI mice and LPS-treated HK2 cells were upregulated compared with the control group. Overexpression of ANRIL increased apoptosis and promoted TLR4 (Toll-like receptor 4), NF-κB phosphorylation, and downstream transcription factor production. Conclusion: ANRIL/NF-κB pathway in LPS-induced apoptosis provided theoretical guidance for ANRIL in the treatment of AKI.

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