Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous pollutants that are metabolized to carcinogenic dihydrodiol epoxides (PAHDE) by cytochrome P450 1B1 (CYP1B1). This metabolism occurs in bone marrow (BM) mesenchymal stem cells (MSC), which sustain hematopoietic stem and progenitor cells (HSPC). In BM, CYP1B1-mediated metabolism of 7, 12-dimethylbenz[a]anthracene (DMBA) suppresses HSPC colony formation within 6 h, whereas benzo(a)pyrene (BP) generates protective cytokines. MSC, enriched from adherent BM cells, yielded the bone marrow stromal, BMS2, cell line. These cells express elevated basal CYP1B1 that scarcely responds to Ah receptor (AhR) inducers. BMS2 cells exhibit extensive transcriptome overlap with leptin receptor positive mesenchymal stem cells (Lepr+ MSC) that control the hematopoietic niche. The overlap includes CYP1B1 and the expression of HSPC regulatory factors (Ebf3, Cxcl12, Kitl, Csf1 and Gas6). MSC are large, adherent fibroblasts that sequester small HSPC and macrophage in the BM niche (Graphic abstract). High basal CYP1B1 expression in BMS2 cells derives from interactions between the Ah-receptor enhancer and proximal promoter SP1 complexes, boosted by autocrine signaling. PAH effects on BMS2 cells model Lepr+MSC niche activity. CYP1B1 metabolizes DMBA to PAHDE, producing p53-mediated mRNA increases, long after the in vivo HSPC suppression. Faster, direct p53 effects, favored by stem cells, remain possible PAHDE targets. However, HSPC regulatory factors remained unresponsive. BP is less toxic in BMS2 cells, but, in BM, CYP1A1 metabolism stimulates macrophage cytokines (Il1b > Tnfa> Ifng) within 6 h. Although absent from BMS2 and Lepr+MSC, their receptors are highly expressed. The impact of this cytokine signaling in MSC remains to be determined.
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http://dx.doi.org/10.1016/j.taap.2020.115111 | DOI Listing |
J Clin Immunol
December 2024
Pediatric Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, University of Bologna, Bologna, Italy.
Background: Activated Phosphoinositide 3-Kinase (PI3K) δ Syndrome (APDS), an inborn error of immunity due to upregulation of the PI3K pathway, leads to recurrent infections and immune dysregulation (lymphoproliferation and autoimmunity).
Methods: Clinical and genetic data of 28 APDS patients from 25 unrelated families were collected from fifteen Italian centers.
Results: Patients were genetically confirmed with APDS-1 (n = 20) or APDS-2 (n = 8), with pathogenic mutations in the PIK3CD or PIK3R1 genes.
Methods Mol Biol
December 2024
Department of Experimental Medicine, Biotechnology, and Molecular Biology Section, Luigi Vanvitelli Campania University, Naples, Italy.
Mesenchymal stromal cells (MSCs) are a heterogeneous population of non-hematopoietic adult stem cells derived from the embryonic mesoderm. They possess self-renewal and multipotent differentiation capabilities, allowing them to give rise to mesodermal cell types, such as osteoblasts, chondroblasts, and adipocytes, as well as non-mesodermal cells, including neuron-like cells and endothelial cells. MSCs play a vital role in maintaining homeostasis across various tissues by facilitating tissue repair, immune regulation, and inflammatory response balance.
View Article and Find Full Text PDFHistochem Cell Biol
December 2024
Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Hematopoietic stem cells (HSCs) reside in a milieu that supports their functions, differentiation, and survival. This niche consists of several types of cells, including mesenchymal stem/stromal cells, endothelial cells, osteoblasts, megakaryocytes, macrophages, adipocytes, lymphoid cells, and nerve fibers. The interactions between these cells and HSCs have a role in HSC fate.
View Article and Find Full Text PDFInfect Immun
December 2024
Laboratory of Applied Immunology, Institute of Biology Sciences, University of Brasília, Brasília, Brazil.
Dormancy is an adaptation in which cells reduce their metabolism, transcription, and translation to stay alive under stressful conditions, preserving the capacity to reactivate once the environment reverts to favorable conditions. Dormancy and reactivation of () are closely linked to intracellular residency within macrophages. Our previous work showed that murine macrophages rely on the viable but not cultivable (VBNC-a dormancy phenotype) fungus from active , with striking differences in immunometabolic gene expression.
View Article and Find Full Text PDFJMIR Res Protoc
December 2024
Division of Pediatric Hematology-Oncology, Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL, United States.
Background: Pediatric patients with cancer have limited options to self-manage their health while they are undergoing treatments in the hospital and after they are discharged to their homes. Extended reality (ER) using head-mounted displays has emerged as an immersive method of improving pain and mental health and promoting health-enhancing physical activity among a variety of clinical groups, but there is currently no established protocol for improving both physical and mental health in pediatric cancer rehabilitation.
Objective: This phase I, pilot, feasibility randomized controlled trial aims to investigate the potential effects of a 14-week ER program on physical activity participation and indicators of health among pediatric patients with cancer who undergo bone marrow transplantation.
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