AI Article Synopsis
- The study found that HMGB1, a nuclear protein, represses HIV-1 gene expression specifically in epithelial cells by inhibiting transcription from the long terminal repeat (LTR) region.
- HMGB1's inhibitory effects were not seen with other viral promoters, and its impact on HIV-1 subtype C was linked to the presence of NF kappa B sites in the LTR.
- In HeLa and monocytic cells, decreased HMGB1 levels increased viral replication, while in unstimulated Jurkat cells, HMGB1 expression did not influence HIV-1 replication.
Article Abstract
We investigated whether the high mobility group B 1 (HMGB1), an abundant nuclear protein in all mammalian cells, affects HIV-1 transcription. Intracellular expression of human HMGB1 repressed HIV-1 gene expression in epithelial cells. This inhibitory effect of HMGB1 was caused by repression of long terminal repeat (LTR)-mediated transcription. Other viral promoters/enhancers, including simian virus 40 or cytomegalovirus, were not inhibited by HMGB1. In addition, HMGB1 inhibition of HIV-1 subtype C expression was dependent on the number of NF kappa B sites in the LTR region. The inhibitory effect of HMGB1 on viral gene expression observed in HeLa cells was confirmed by an upregulation of viral replication in the presence of antisense HMGB1 in monocytic cells. In contrast to what was found in HeLa cells and monocytic cells, endogenous HMGB1 expression did not affect HIV-1 replication in unstimulated Jurkat cells. Thus, intracellular HMGB1 affects HIV-1 LTR-directed transcription in a promoter- and cell-specific manner.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/s0042-6822(03)00453-7 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Dual alarmin-receptor-specific targeting peptide systems for treatment of sepsis.
Acta Pharm Sin B
December 2024
Department of Molecular and Life Science, Hanyang University, Ansan 15588, Republic of Korea.
The pathophysiology of sepsis is characterized by a systemic inflammatory response to infection; however, the cytokine blockade that targets a specific early inflammatory mediator, such as tumor necrosis factor, has shown disappointing results in clinical trials. During sepsis, excessive endotoxins are internalized into the cytoplasm of immune cells, resulting in dysregulated pyroptotic cell death, which induces the leakage of late mediator alarmins such as HMGB1 and PTX3. As late mediators of lethal sepsis, overwhelming amounts of alarmins bind to high-affinity TLR4/MD2 and low-affinity RAGE receptors, thereby amplifying inflammation during early-stage sepsis.
View Article and Find Full Text PDFTumor Vaccine Exploiting Membranes with Influenza Virus-Induced Immunogenic Cell Death to Decorate Polylactic Coglycolic Acid Nanoparticles.
ACS Nano
January 2025
Laboratory of Molecular Immunology, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming 650031, China.
Immunogenic cell death (ICD) of tumor cells, which is characterized by releasing immunostimulatory "find me" and "eat me" signals, expressing proinflammatory cytokines and providing personalized and broad-spectrum tumor antigens draws increasing attention in developing a tumor vaccine. In this study, we aimed to investigate whether the influenza virus (IAV) is efficient enough to induce ICD in tumor cells and an extra modification of IAV components such as hemeagglutinin (HA) will be helpful for the ICD-induced cells to elicit robust antitumor effects; in addition, to evaluate whether the membrane-engineering polylactic coglycolic acid nanoparticles (PLGA NPs) simulating ICD immune stimulation mechanisms hold the potential to be a promising vaccine candidate, a mouse melanoma cell line (B16-F10 cell) was infected with IAV rescued by the reverse genetic system, and the prepared cells and membrane-modified PLGA NPs were used separately to immunize the melanoma-bearing mice. IAV-infected tumor cells exhibit dying status, releasing high mobility group box-1 (HMGB1) and adenosine triphosphate (ATP), and exposing calreticulin (CRT), IAV hemeagglutinin (HA), and tumor antigens like tyrosinase-related protein 2 (TRP2).
View Article and Find Full Text PDF[Mechanism of chrysophanol in inhibiting ox-LDL-induced macrophage foaminess through NF-κB/HMGB1-PI3K/Akt/mTOR pathway].
Zhongguo Zhong Yao Za Zhi
December 2024
School of Basic Medical Sciences, Guangzhou University of Chinese Medicine Guangzhou 511400, China.
The aim of this study was to investigate the underlying mechanism of chrysophanol(Chr) in reducing inflammation and foam cell formation induced by oxidized low-density lipoprotein(ox-LDL) and to investigate the targets and pathways related to effects of Chr on coronary atherosclerosis, providing a theoretical basis for the development of new clinical drugs. RAW264.7 macrophages were cultured in vitro, and after determining the appropriate concentrations of Chr and ox-LDL for treating RAW264.
View Article and Find Full Text PDFHMGB1 mediates epithelial-mesenchymal transition and fibrosis in silicosis via RAGE/β-catenin signaling.
Chem Biol Interact
January 2025
Hebei Key Laboratory of Organ Fibrosis, School of Public Health, North China University of Science and Technology, Tangshan, Hebei 063210, China. Electronic address:
Epithelial-mesenchymal transition (EMT) is implicated in the pathogenesis of silicosis. High mobility group box 1 (HMGB1) has been found to induce EMT in fibrotic diseases. Previous studies have revealed a critical role of HMGB1 in silicosis, whereas the detail mechanisms still obscure.
View Article and Find Full Text PDFMolecular biomarkers of glial activation and injury in epilepsy.
Drug Discov Today
January 2025
Faculty of Engineering and Science, University of Greenwich London, Chatham Maritime, ME4 4TB, UK; Faculty of Medicine, Tbilisi State University, Tbilisi 0179, Georgia. Electronic address:
Increasing evidence from fluid biopsies suggests activation and injury of glial cells in epilepsy. The prevalence of clinical and subclinical seizures in neurodegenerative conditions such as Alzheimer's disease, frontotemporal dementia, and others merits review and comparison of the effects of seizures on glial markers in epilepsy and neurodegenerative diseases with concomitant seizures. Herein, we revisit preclinical and clinical reports of alterations in glial proteins in cerebrospinal fluid and blood associated with various types of epilepsy.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!