Author ORCID Identifier
https://orcid.org/0000-0002-7625-3341
https://orcid.org/0000-0002-5162-2761
https://orcid.org/0000-0003-1640-1928
N/A
https://orcid.org/0000-0003-1321-1520
https://orcid.org/0000-0001-8916-4092
N/A
Document Type
Article
Publication Date
2010
College/Unit
School of Medicine
Department/Program/Center
Pediatrics
Abstract
Background
The host's response to infection is characterized by altered levels of neurotrophins and an influx of inflammatory cells to sites of injured tissue. Progenitor cells that give rise to the differentiated cellular mediators of inflammation are derived from bone marrow progenitor cells where their development is regulated, in part, by cues from bone marrow stromal cells (BMSC). As such, alteration of BMSC function in response to elevated systemic mediators has the potential to alter their function in biologically relevant ways, including downstream alteration of cytokine production that influences hematopoietic development.
Methodology/Principal Findings
In the current study we investigated BMSC neurotrophin receptor expression by flow cytometric analysis to determine differences in expression as well as potential to respond to NGF or BDNF. Intracellular signaling subsequent to neurotrophin stimulation of BMSC was analyzed by western blot, microarray analysis, confocal microscopy and real-time PCR. Analysis of BMSC Interleukin-6 (IL-6) expression was completed using ELISA and real-time PCR.
Conclusion
BMSC established from different individuals had distinct expression profiles of the neurotrophin receptors, TrkA, TrkB, TrkC, and p75NTR. These receptors were functional, demonstrated by an increase in Akt-phosphorylation following BMSC exposure to recombinant NGF or BDNF. Neurotrophin stimulation of BMSC resulted in increased IL-6 gene and protein expression which required activation of ERK and p38 MAPK signaling, but was not mediated by the NFκB pathway. BMSC response to neurotrophins, including the up-regulation of IL-6, may alter their support of hematopoiesis and regulate the availability of inflammatory cells for migration to sites of injury or infection. As such, these studies are relevant to the growing appreciation of the interplay between neurotropic mediators and the regulation of hematopoiesis.
Digital Commons Citation
Rezaee, Fariba; Rellick, Stephanie L.; Piedimonte, Giovanni; Akers, Stephen M.; O'Leary, Heather A.; Martin, Karen; Craig, Michael D.; and Gibson, Laura F., "Neurotrophins Regulate Bone Marrow Stromal Cell IL-6 Expression through the MAPK Pathway" (2010). Faculty & Staff Scholarship. 2798.
https://researchrepository.wvu.edu/faculty_publications/2798
Source Citation
Rezaee F, Rellick SL, Piedimonte G, Akers SM, O'Leary HA, Martin K, et al. (2010) Neurotrophins Regulate Bone Marrow Stromal Cell IL-6 Expression through the MAPK Pathway. PLoS ONE 5(3): e9690. https://doi.org/10.1371/journal.pone.0009690
Comments
© 2010 Rezaee et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.