Related Experiment Video
Updated: Jun 14, 2026
07:38
Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants
Published on: June 6, 2025
Neurotrophins regulate bone marrow stromal cell IL-6 expression through the MAPK pathway
Fariba Rezaee1, Stephanie L Rellick, Giovanni Piedimonte
1Department of Pediatrics, West Virginia University School of Medicine, Morgantown, West Virginia, United States of America.
Plos One
|March 20, 2010
Summary
Bone marrow stromal cells (BMSC) express functional neurotrophin receptors. Neurotrophin stimulation increases IL-6 production, potentially impacting hematopoiesis and inflammatory cell migration.
Area of Science:
- Neuroscience
- Immunology
- Hematology
Background:
- Host response to infection involves neurotrophins and inflammatory cells.
- Bone marrow stromal cells (BMSC) regulate hematopoietic development.
- Altered BMSC function can impact cytokine production and hematopoiesis.
Purpose of the Study:
- Investigate BMSC neurotrophin receptor expression and function.
- Determine BMSC response to nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF).
- Analyze the impact of neurotrophin stimulation on Interleukin-6 (IL-6) production in BMSC.
Main Methods:
- Flow cytometry for neurotrophin receptor expression.
- Western blot, microarray, confocal microscopy, and real-time PCR for intracellular signaling.
- ELISA and real-time PCR for IL-6 expression analysis.
Main Results:
- BMSC from different individuals showed distinct neurotrophin receptor profiles (TrkA, TrkB, TrkC, p75(NTR)).
- Neurotrophin stimulation increased Akt-phosphorylation, indicating functional receptors.
- Increased IL-6 gene and protein expression occurred via ERK and p38 MAPK pathways, not NFkappaB.
Conclusions:
- BMSC neurotrophin receptors are functional and influence IL-6 production.
- Neurotrophin-induced IL-6 upregulation in BMSC may affect hematopoiesis.
- These findings highlight the interplay between neurotrophic mediators and hematopoietic regulation.
Related Concept Videos
02:26NF-κB-dependent Signaling Pathway
The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...
01:07MAPK Signaling Cascades
Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
01:01Regulation of Hematopoietic Stem Cells
All blood and immune cells are produced from the multipotent hematopoietic stem cells (HSCs) by the process of hematopoiesis. However, they all have a limited life span. In addition, many are depleted in immune surveillance or combatting an injury or infection. This makes blood one of the most regenerative tissues. Hematopoiesis helps replenish these blood and immune cells, restoring the body's normal functioning. However, overproduction of blood and immune cells can make them cancerous or...
01:20The JAK-STAT Signaling Pathway
Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as SH2...
01:16TGF - β Signaling Pathway
The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors are of three kinds RI, RII, and RIII. The RI...
01:24T Cell Types and Functions
When T cells with CD4 markers are activated, they give rise to two types of effector cells: helper T cells and regulatory T cells. Meanwhile, T cells with CD8 markers differentiate into effector cytotoxic T cells. The differentiation of CD4 T cells into helper T cell subsets, such as Th1, Th2, and Th17 cells, is dependent on the antigen type, antigen-presenting cell, and regulatory cytokines.
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...