Natural killer T (NKT) lymphocyte cells are a subset of regulatory lymphocytes with important immunemodulatory effects. Our aim was to evaluate the effect of transplantation of NKT lymphocytes on graft versus host disease (GVHD) in a murine model of semiallogeneic BMT. GVHD was generated by infusion of 2 x 107 splenocytes from C57BL/6 donor mice into irradiated (C57BL/6 x Balb/c)F1 recipient mice. Adoptive transfer of increasing numbers of DX5+ cells was performed. Recipient mice were followed for histological parameters of GVHD-associated liver, bowel, and cutaneous injury. Intrahepatic and intrasplenic lymphocytes were isolated and analyzed by FACS for CD4+ and CD8+ subpopulations. It was seen that adoptive transfer of 4.5 x 106 DX5+ cells significantly alleviated GVHD-related hepatic, bowel, and cutaneous injury, and improved survival (85% survival on day 28). In contrast, depletion of DX5+ cells led to severe GVHD-associated multiorgan injury and 100% mortality. A direct correlation with the number of transplanted DX5+ cells was noted (maximal effect with transplantation of 4.5 x 106 DX5+ cells). Tolerance induction was associated with an increased peripheral CD4/CD8 ratio, intrahepatic trapping of CD8 lymphocytes and a shift towards a Th2-type cytokine profile, manifested by decreased IL-12/IL10, IL-12/IL-4, IFNgamma/IL-10, and IFNgamma/IL-4 ratios. Transplantation of DX5+ cells holds promise as a novel therapeutic measure for GVHD.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1038/sj.bmt.1704719 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
c-MET tyrosine kinase inhibitors reverse drug resistance mediated by the ATP-binding cassette transporter B1 (ABCB1) in cancer cells.
3 Biotech
January 2025
Medicinal and Natural Products Chemistry Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
This study investigated the potential of MET kinase inhibitors, cabozantinib, crizotinib, and PHA665752, in reversing multidrug resistance (MDR) mediated by ABCB1 in cancer cells. The accumulation of the fluorescent probe, Rhodamine 123, was assessed using flow cytometry and fluorescence microscopy in MDR MES-SA/DX5 and parental cells. The growth inhibitory activity of MET inhibitors as monotherapies and in combination with chemotherapeutic drugs was evaluated by MTT assay.
View Article and Find Full Text PDFOrganometallic Half-Sandwich Complexes of 8-Hydroxyquinoline-Derived Mannich Bases with Enhanced Solubility: Targeting Multidrug Resistant Cancer.
Inorg Chem
December 2024
MTA-SZTE Lendület Functional Metal Complexes Research Group, University of Szeged, Dóm tér 7-8, Szeged H-6720 , Hungary.
Drug resistance is a major obstacle in cancer treatment. Herein, four novel organometallic complexes, with the general formula [Ru(η--cymene)(HL)Cl]Cl and [Rh(η-CMe)(HL)Cl]Cl, were developed to target multidrug-resistant (MDR) cancer cells, where HL denotes 8-hydroxyquinoline-derived Mannich bases (HQCl-pyr and HQCl-pip). The aim of the complexation was to obtain compounds with improved drug-like properties.
View Article and Find Full Text PDFNAP1L1 Promotes Endometrial Cancer Progression via EP300-Mediated DDX5 Promoter Acetylation.
Mol Cancer Res
November 2024
Department of Obstetrics and Gynecology, The First Affiliated Hospital of Soochow University, Suzhou, People's Republic of China.
Endometrial cancer is one of the predominant tumors of the female reproductive system. In this current study, we investigated the functions and related mechanisms of nucleosome assembly protein 1 like 1 (NAP1L1)/ DEAD-box helicase 5 (DDX5) in endometrial cancer. This retrospective study analyzed the medical records of patients with endometrial cancer, collected tissue samples for NAP1L1 and DDX5 staining, and conducted survival analysis using the Kaplan-Meier method.
View Article and Find Full Text PDFCopper(II) Complexes with Isomeric Morpholine-Substituted 2-Formylpyridine Thiosemicarbazone Hybrids as Potential Anticancer Drugs Inhibiting Both Ribonucleotide Reductase and Tubulin Polymerization: The Morpholine Position Matters.
J Med Chem
June 2024
Institute of Inorganic Chemistry, University of Vienna, Vienna A-1090, Austria.
Article Synopsis
- The study investigates copper(II) thiosemicarbazone complexes as potential anticancer agents, targeting both ribonucleotide reductase (RNR) and tubulin polymerization.
- The researchers synthesized and characterized four proligands with a methylmorpholine substituent, noting how the position of this group influences the complexes' efficacy against cancer cells.
- Findings indicate that the complexes effectively inhibit key cancer-related processes, with their antiproliferative activity tied to mechanisms that quench a radical in RNR and impede tubulin polymerization.
Methyl-Jasmonate Functions as a Molecular Switch Promoting Cross-Talk between Pathways for the Biosynthesis of Isoprenoid Backbones Used to Modify Proteins in Plants.
Plants (Basel)
April 2024
Centre National de la Recherche Scientifique, Institut de Biologie Moléculaire des Plantes (IBMP), Université de Strasbourg, 12 rue du Général Zimmer, F-67084 Strasbourg, France.
In plants, the plastidial mevalonate (MVA)-independent pathway is required for the modification with geranylgeranyl groups of CaaL-motif proteins, which are substrates of protein geranylgeranyltransferase type-I (PGGT-I). As a consequence, fosmidomycin, a specific inhibitor of 1-deoxy-d-xylulose (DX)-5 phosphate reductoisomerase/DXR, the second enzyme in this so-called methylerythritol phosphate (MEP) pathway, also acts as an effective inhibitor of protein prenylation. This can be visualized in plant cells by confocal microscopy by expressing GFP-CaM-CVIL, a prenylation sensor protein.
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!