Glucocorticoid hormones, calcium ionophores and anti-CD3 monoclonal antibodies induce apoptosis in mouse thymocytes. This type of cell death, which is characterized by an extensive DNA fragmentation into oligonucleosomal subunits, occurs in the intrathymic process of negative selection, and is involved in the deletion of autoreactive T-cells during thymic maturation. A number of cytokines are able to modulate apoptosis, and interleukins, including interleukin-1, interleukin-2, and interleukin-4, play a crucial role in thymic maturation and T-cell development. We tested the effects of several cytokines on the glucocorticoid hormone-induced apoptosis of mouse thymocytes in vitro, and demonstrated that interleukin-1 alpha, interleukin-2, and interleukin-4 inhibit the apoptosis induced by dexamethasone, but that interleukin-3 and interleukin-6 exert no noteworthy effect. Dose-response experiments indicated that interleukin-4 is more potent than interleukin-1 alpha and interleukin-2 in inhibiting dexamethasone-induced apoptosis. Furthermore, interleukin-4 fully inhibited the DNA fragmentation induced by the protein kinase-C activator 12-O-tetradecanoylphorbol-13-acetate, but was ineffective against apoptosis induced by the calcium ionophore A23187. These results suggest that interleukins regulate the thymic selection process by acting as modulators of the negative selection process.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1007/BF02591666 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Induction of M1 polarization in BV2 cells by propofol intervention promotes perioperative neurocognitive disorders through the NGF/CREB signaling pathway: an experimental research.
Int J Surg
January 2025
Department of Anesthesiology, Jiangxi Cancer Hospital & Institute, Jiangxi Clinical Research Center for Cancer, The Second Affiliated Hospital of Nanchang Medical College, Jiangxi Key Laboratory of Oncology, Nanchang, Jiangxi Province, China.
Nerve growth factor (NGF) is critical in regulating the homeostasis of microglial cells. It activates various signaling pathways that mediate the phosphorylation of cAMP response element-binding protein (CREB) at key regulatory sites. The decrease in phosphorylated CREB (p-CREB) expression is linked to neuroinflammatory responses.
View Article and Find Full Text PDFDesign of ROS-Triggered Sesquiterpene Lactone SC Prodrugs as TrxR1 Covalent Inhibitors for the Treatment of Non-Small Cell Lung Cancer.
J Med Chem
January 2025
Key Laboratory of Computational Chemistry-Based Natural Antitumor Drug Research & Development, Liaoning Province; Engineering Research Center of Natural Medicine Active Molecule Research & Development, Liaoning Province; Key Laboratory of Natural Bioactive Compounds Discovery & Modification, Shenyang; School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, China.
Thioredoxin reductase 1 (TrxR1) is an important therapeutic target for nonsmall cell lung cancer (NSCLC) treatment due to its overexpression in NSCLC cells. In this work, to address the deficiency that sesquiterpene lactone containing α-methylene-γ-lactone moiety was rapidly metabolized by endogenous nucleophiles, series of novel thioether derivatives were designed and synthesized based on a reactive oxygen species (ROS)-triggered prodrug strategy. Among them, prodrug exhibited potent cytotoxicity against NSCLC cells and better release rates in response to ROS.
View Article and Find Full Text PDFZinc finger protein 169 promotes tumor progress of hepatocellular cancer via up-regulating cyclin-dependent kinase 19.
IUBMB Life
January 2025
Senior Department of Hepatology, the Fifth Medical Center of Chinese PLA General Hospital, Beijing, China.
Hepatocellular carcinoma (HCC) ranks among the most prevalent types of cancer globally. Zinc finger protein 169 (ZNF169) holds significant importance as a transcription factor, yet its precise function in HCC remains to be elucidated. This study aims to examine the clinical importance, biological functions, and molecular pathways associated with ZNF169 in the development of HCC.
View Article and Find Full Text PDFRationale: WW domain-containing oxidoreductase ( ) is a gene associated implicated in both neurologic and inflammatory diseases and is susceptible to environmental stressors. We hypothesize partial loss of Wwox function will result in increased sepsis severity and neuroinflammation.
Methods: mice, generated by CRISPR/Cas9, and mice were treated with intraperitoneal PBS vs LPS (10mg/kg) and euthanized 12 hours post-injection.
Esketamine at a Clinical Dose Attenuates Cerebral Ischemia/Reperfusion Injury by Inhibiting AKT Signaling Pathway to Facilitate Microglia M2 Polarization and Autophagy.
Drug Des Devel Ther
January 2025
Department of Anesthesiology, Beijing Friendship Hospital, Capital Medical University, Beijing, People's Republic of China.
Purpose: This study aimed to assess the protective effect of a clinical dose esketamine on cerebral ischemia/reperfusion (I/R) injury and to reveal the potential mechanisms associated with microglial polarization and autophagy.
Methods: Experimental cerebral ischemia was induced by middle cerebral artery occlusion (MCAO) in adult rats and simulated by oxygen-glucose deprivation (OGD) in BV-2 microglial cells. Neurological and sensorimotor function, cerebral infarct volume, histopathological changes, mitochondrial morphological changes, and apoptosis of ischemic brain tissues were assessed in the presence or absence of esketamine and the autophagy inducer rapamycin.
Want 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!