scholarly journals 2-O-Methylhonokiol Suppresses HCV Replication via TRAF6-Mediated NF-kB Activation

2021 ◽  
Vol 22 (12) ◽  
pp. 6499
Author(s):  
Suyun Jeong ◽  
Young-seok Lee ◽  
Kiyoon Kim ◽  
Ji-su Yoon ◽  
Sungsoo Kim ◽  
...  
Keyword(s):  
Immune Response ◽  
Tumor Necrosis Factor Receptor ◽  
Host Immune Response ◽  
Renilla Luciferase ◽  
Luciferase Assay ◽  
Innate Immune Responses ◽  
Chronic Hcv Infection ◽  
Chronic Hcv ◽  
Light Chain Enhancer ◽  
Necrosis Factor

Hepatitis C virus (HCV) is associated with various liver diseases. Chronic HCV infection is characterized by an abnormal host immune response. Therefore, it is speculated that to suppress HCV, a well-regulated host immune response is necessary. 2-O-methylhonokiol was identified by the screening of anti-HCV compounds using Renilla luciferase assay in Huh 7.5/Con 1 genotype 1b replicon cells. Here, we investigated the mechanism by which 2-O-methylhonokiol treatment inhibits HCV replication using real-time PCR. Our data shows that treatment with 2-O-methylhonokiol activated innate immune responses via nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) pathway. Additionally, the immunoprecipitation result shows that treatment with 2-O-methylhonokiol augmented tumor necrosis factor receptor (TNFR)-associated factor 6 (TRAF6) by preventing p62 from binding to TRAF6, resulting in reduced autophagy caused by HCV. Finally, we reproduced our data with the conditioned media from 2-O-methylhonokiol-treated cells. These findings strongly suggest that 2-O-methylhonokiol enhances the host immune response and suppresses HCV replication via TRAF6-mediated NF-kB activation.

scholarly journals Newer molecules and new hopes in the management of chronic hepatitis C

JMS SKIMS ◽  
2010 ◽  
Vol 13 (2) ◽  
pp. 39-40
Author(s):  
Showkat Ali Zargar
Keyword(s):  
Hepatocellular Carcinoma ◽  
Immune Response ◽  
Liver Transplantation ◽  
Chronic Hepatitis ◽  
Hepatitis C ◽  
Chronic Hepatitis C ◽  
Chronic Infection ◽  
Antiviral Therapies ◽  
Chronic Hcv Infection ◽  
Chronic Hcv

Chronic hepatitis C is highly prevalent with prevalence rate of around 3% involving about 180 million people worldwide, despite major advances in its understanding of viral 1 pathogenesis and significant evolution in antiviral therapies. Most of the patients develop chronic infection because the virus evades the host immune response in majority of patients. Chronic HCV infection can lead to cirrhosis and hepatocellular carcinoma. Complications of HCV-related cirrhosis are the leading indication for liver transplantation in United States and Europe...... J Med Sci 2010;13(2): 39-40.

scholarly journals Tumor Necrosis Factor Receptor 1 Expression Is Upregulated in Dendritic Cells in Patients with Chronic HCV Who Respond to Therapy

2010 ◽  
Vol 2010 ◽  
pp. 1-10
Author(s):  
Raul Cubillas ◽  
Katherine Kintner ◽  
Frances Phillips ◽  
Nitin J. Karandikar ◽  
Dwain L. Thiele ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Mononuclear Cells ◽  
Tumor Necrosis Factor Receptor ◽  
Mrna Levels ◽  
Specific Subset ◽  
Significant Difference ◽  
Chronic Hcv ◽  
Necrosis Factor

The present studies assessed the level of tumor necrosis factor receptor (TNFR) expression in peripheral blood mononuclear cells (PBMCs) subsets from patients with chronic HCV undergoing interferon /ribavirin-based therapy (Ifn/R). Methods. TNFR family member mRNA expression was determined using quantitative real-time PCR assays (RTPCRs) in PBMC from 39 HCV+ patients and 21 control HCV patients. Further subset analysis of HCV + patients (untreated (U), sustained virological responders (SVR), and nonresponders (NR)/relapsers (Rel)) PBMC was performed via staining with anti-CD123, anti-CD33, anti-TNFR1 or via RTPCR for TNFR1 mRNA. Results. A similar level of TNFR1 mRNA in PBMC from untreated HCV+ genotype 1 patients and controls was noted. TNFR1 and TNFR2 mRNA levels in PBMC from HCV+ patients with SVR were statistically different than levels in HCV() patients. A significant difference was noted between the peak values of TNFR1 of the CD123+ PBMC isolated from SVR and the NR/Rel. Conclusion. Upregulation of TNFR1 expression, occurring in a specific subset of CD123+ dendritic cells, appeared in HCV+ patients with SVR.

scholarly journals New Horizons and Perspectives in the Management of Chronic Hepatitis C

JMS SKIMS ◽  
2010 ◽  
Vol 13 (2) ◽  
pp. 41-47
Author(s):  
Jaswinder Singh Sodhi ◽  
Shaheena Parveen ◽  
Riyaz U Saif
Keyword(s):  
United States ◽  
Immune Response ◽  
Liver Transplantation ◽  
Chronic Hepatitis ◽  
Hepatitis C ◽  
Chronic Infection ◽  
New Horizons ◽  
Chronic Hcv Infection ◽  
Chronic Hcv ◽  
Cellular Carcinoma

Hepatitis-C virus (HCV) infects 170 million people, 1 with worldwide sero prevalence of around 3%. Most of the patients develop chronic infection because the virus evades the host immune response in 55-85% of patients. Chronic HCV infection can lead to cirrhosis and hepato-cellular carcinoma. Complications of HCV-related cirrhosis are the leading indication for liver transplantation in United States and Europe... J Med Sci 2010;13(2):41-47

Evaluation of the immune response in patients with chronic HCV infection

2006 ◽  
Vol 22 (2) ◽  
Author(s):  
Mahmoud Ismail Hassan ◽  
Samar Kamal Kassim ◽  
Maha Imam Ahmed ◽  
Ali Khalifa
Keyword(s):  
Immune Response ◽  
Hcv Infection ◽  
Chronic Hcv Infection ◽  
Chronic Hcv

scholarly journals Role of Tumor Necrosis Factor Alpha in Helicobacter pylori Gastritis in Tumor Necrosis Factor Receptor 1-Deficient Mice

2002 ◽  
Vol 70 (6) ◽  
pp. 3149-3155 ◽  
Author(s):  
Ulrike Thalmaier ◽  
Norbert Lehn ◽  
Klaus Pfeffer ◽  
Manfred Stolte ◽  
Michael Vieth ◽  
...  
Keyword(s):  
Immune Response ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Receptor ◽  
Necrosis Factor Alpha ◽  
Humoral Immune ◽  
Tnf Α ◽  
Factor Alpha ◽  
H Pylori ◽  
Necrosis Factor

ABSTRACT Increased gastric production of interleukin 8 and tumor necrosis factor alpha (TNF-α) has been implicated in the pathogenesis of Helicobacter pylori-associated gastroduodenal disease. In the present study we used a mouse model to demonstrate whether loss of the tumor necrosis factor receptor 1 (TNF-R1) function leads to differences in gastric inflammation or the systemic immune response in H. pylori infection. Six different clinical isolates of H. pylori (three cytotoxin-positive and three cytotoxin-negative strains) were adapted to C57BL/6 mice. TNF-R1-deficient (TNF-R1−/−) mice (n = 19) and isogenetic controls (n = 24) were infected and sacrificed after 4 weeks of infection. Inflammation of the stomach and the humoral immune response to H. pylori were evaluated by histological, immunohistochemical, and serological methods. There was no detectable difference in the grade or activity of gastritis in TNF-R1−/− mice when they were compared with wild-type mice, but the number of lymphoid aggregates was slightly reduced in the gastric mucosa of TNF-R1−/− mice. Interestingly, total immunoglobulin G (IgG), as well as IgG1, IgG2b, and IgG3, H. pylori-specific antibody titers were significantly higher in wild-type mice. As revealed by immunoblot analysis, the difference in reactivity against H. pylori antigens was not based on a failure to recognize single H. pylori antigens in TNF-R1−/− mice. We therefore suggest that TNF-R1-mediated TNF-α signals might support a systemic humoral immune response against H. pylori and that the gastric inflammatory response to H. pylori infection seems to be independent of TNF-R1-mediated signals.

scholarly journals YTHDF1 drives intestinal immune response against bacterial infection

2020 ◽  
Author(s):  
Xin Zong ◽  
Xiao Xiao ◽  
Bin Shen ◽  
Qin Jiang ◽  
Hong Wang ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Bacterial Infection ◽  
Pathogenic Bacteria ◽  
Stop Codon ◽  
Tumor Necrosis Factor Receptor ◽  
Underlying Mechanism ◽  
Innate Immune Responses ◽  
Key Driver ◽  
Unique Mechanism

AbstractInvasion of pathogenic bacteria is a serious threat to intestinal health. Recent emerging evidence has demonstrated that N6-methyladenosine (m6A) is closely associated with innate immunity; however, the underlying mechanism remains unclear. Herein, we aim to explore the function and mechanism of m6A modification in the regulation of innate immune responses against bacterial pathogens in the intestine. Ribo-seq and m6A-seq data have demonstrated that YTHDF1, an m6A reader, directs the translation of tumor necrosis factor receptor-associated factor 6 (TRAF6) mRNA to regulate immune responses via modulation of m6A methylation near stop codon. Furthermore, we have identified a unique mechanism that the interaction between YTHDF1 and the host factor DDX60 are critical in regulating intestinal immune response against bacterial infection by recognizing TRAF6 target transcripts. Additionally, our results provide novel insights as to why YTHDF1 could recognize its unique targets using the same domain as other YTHDF proteins. This work identifies YTHDF1 as a key driver of intestinal immune responses and provides an avenue for development of novel strategies to modulate intestinal immune response against bacterial infection.

scholarly journals c-Jun N-Terminal Kinase 1 Is Required for Toll-Like Receptor 1 Gene Expression in Macrophages

2007 ◽  
Vol 75 (10) ◽  
pp. 5027-5034 ◽  
Author(s):  
Hooman Izadi ◽  
Amirreza T. Motameni ◽  
Tonya C. Bates ◽  
Elias R. Olivera ◽  
Vega Villar-Suarez ◽  
...  
Keyword(s):  
Immune Response ◽  
Innate Immune Response ◽  
Feedback Loop ◽  
Innate Immune ◽  
Proximal Promoter ◽  
Innate Immune Responses ◽  
Necrosis Factor Alpha ◽  
Factor Alpha ◽  
Molecular Patterns ◽  
Necrosis Factor

ABSTRACT The regulation of innate immune responses to pathogens occurs through the interaction of Toll-like receptors (TLRs) with pathogen-associated molecular patterns and the activation of several signaling pathways whose contribution to the overall innate immune response to pathogens is poorly understood. We demonstrate a mechanism of control of murine macrophage responses mediated by TLR1/2 heterodimers through c-Jun N-terminal kinase 1 (JNK1) activity. JNK controls tumor necrosis factor alpha production and TLR-mediated macrophage responses to Borrelia burgdorferi, the causative agent of Lyme disease, and the TLR1/TLR2-specific agonist PAM3CSK4. JNK1, but not JNK2, activity regulates the expression of the tlr1 gene in the macrophage cell line RAW264.7, as well as in primary CD11b+ cells. We also show that the proximal promoter region of the human tlr1 gene contains an AP-1 binding site that is subjected to regulation by the kinase and binds two complexes that involve the JNK substrates c-Jun, JunD, and ATF-2. These results demonstrate that JNK1 regulates the response to TLR1/2 ligands and suggest a positive feedback loop that may serve to increase the innate immune response to the spirochete.

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