Initiation of adaptive immunity requires activation of dendritic cells (DC) by "danger" signals. This study examines the functional consequences of activating a cellular stress response in human DC. Anisomycin, a potent inducer of this "stress" response, selectively activates p38 kinase in DC at low concentrations, and both p38 kinases and JNKs at higher concentrations. Activation of p38, was accompanied by an increase in the potency of dendritic cells to activate T cells. In contrast to LPS, anisomycin had no effect on the expression of several DC activation markers. Anisomycin synergised with LPS in driving release of IL-12 and TNF-alpha. Anisomycin also enhanced the formation of clusters between DC and T cells. Enhanced cytokine release and clustering were both inhibited by the selective p38 alpha and p38 beta inhibitor SB203580. This study demonstrates that the cellular stress response, mediated via p38 kinases, plays an important role in the regulation of several aspects of DC function.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/s0161-5890(02)00262-6 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Identifying Pyroptosis-Hub Genes and Inflammation Cell Type-Related Genes in Ischemic Stroke.
Mol Neurobiol
January 2025
Department of Anesthesiology, Yijishan Hospital, First Affiliated Hospital of Wannan Medical College, Wuhu, 241004, China.
Stroke is the second-leading global cause of death. The damage attributed to the immune storm triggered by ischemia-reperfusion injury (IRI) post-stroke is substantial. However, data on the transcriptomic dynamics of pyroptosis in IRI are limited.
View Article and Find Full Text PDFCopper Chelate Targeting Externalized Phosphatidylserine Inhibits PD-L1 Expression and Enhances Cancer Immunotherapy.
J Am Chem Soc
January 2025
Department of Pharmacy, The First Affiliated Hospital of USTC; Division of Life Sciences and Medicine, University of Science and Technology of China, Anhui Provincial Key Laboratory of Precision Pharmaceutical Preparation and Clinical Pharmacy, Hefei, Anhui 230026, China.
Inhibitors of the PD-1/PD-L1 immune checkpoint have revolutionized cancer treatment. However, the clinical response remains limited, with only 20% of patients benefiting from treatment and approximately 60% of PD-L1-positive patients exhibiting resistance. One key factor contributing to resistance is the externalization of phosphatidylserine (PS) on the surface of cancer cells, which suppresses immune responses and promotes PD-L1 expression, further hindering the efficacy of PD-L1 blockade therapies.
View Article and Find Full Text PDFTumor-Associated Macrophages Nano-Reprogrammers Induce "Gear Effect" to Empower Glioblastoma Immunotherapy.
Small
January 2025
Cancer Hospital of Dalian University of Technology, Dalian University of Technology, Shenyang, 110042, China.
Glioblastoma (GBM), the most malignant brain tumor with high prevalence, remains highly resistant to the existing immunotherapies due to the significant immunosuppression within tumor microenvironment (TME), predominantly manipulated by M2-phenotypic tumor-associated macrophages (M2-TAMs). Here in this work, an M2-TAMs targeted nano-reprogrammers, MG5-S-IMDQ, is established by decorating the mannose molecule as the targeting moiety as well as the toll-like receptor (TLR) 7/8 agonist, imidazoquinoline (IMDQ) on the dendrimeric nanoscaffold. MG5-S-IMDQ demonstrated an excellent capacity of penetrating the blood-brain barrier (BBB) as well as selectively targeting M2-TAMs in the GBM microenvironment, leading to a phenotype transformation and function restoration of TAMs shown as heightened phagocytic activity toward tumor cells, enhanced cytotoxic effects, and improved tumor antigen cross-presentation capability.
View Article and Find Full Text PDFInduces Two Types of Dendritic Cell Activation and Effectively Suppresses Onset of the Common Cold: A Randomized, Double-Blind, Placebo-Controlled Trial.
Nutrients
December 2024
Nihonbashi Cardiology Clinic, Kyodo Bldg. #201, 13-4 Nihonbashi Kodenmacho, Chuo-ku, Tokyo 103-0001, Japan.
Background/objectives: GCL1815 is a lactic acid bacterium thought to activate dendritic cells. This randomized, placebo-controlled, double-blind study aimed to evaluate the effects of GCL1815 on human dendritic cells and the onset of the common cold.
Methods: Two hundred participants were divided into two groups and took capsules containing either six billion GCL1815 cells or placebo for 8 weeks.
Regulation of Age-Related Lipid Metabolism in Ovarian Cancer.
Int J Mol Sci
January 2025
Division of Reproductive Sciences, Department of Obstetrics and Gynecology, Duke University School of Medicine, 701 West Main Street, Suite 510, Duke, P.O. Box 90534, Durham, NC 27701, USA.
The mortality rate of ovarian cancer (OC) remains the highest among female gynecological malignancies. Advanced age is the highest risk factor for OC development and progression, yet little is known about the role of the aged tumor microenvironment (TME). We conducted RNA sequencing and lipidomic analysis of young and aged gonadal adipose tissue from rat xenografts before and after OC formation.
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!