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Characterization and function of histamine receptors in human bone marrow stromal cells.
- Source :
-
Stem cells (Dayton, Ohio) [Stem Cells] 2012 Feb; Vol. 30 (2), pp. 222-31. - Publication Year :
- 2012
-
Abstract
- There are several clinical trials worldwide using bone marrow stromal cells (BMSCs) as a cellular therapy to modulate immune responses in patients suffering from various inflammatory conditions. A deeper understanding of the molecular mechanisms involved in this modulatory effect could help us design better, more effective protocols to treat immune mediated diseases. In this study, we demonstrated that human BMSCs express H1, H2, and H4 histamine receptors and they respond to histamine stimulation with an increased interleukin 6 (IL-6) production both in vitro and in vivo. Using different receptor antagonists, we pinpointed the importance of the H1 histamine receptor, while Western blot analysis and application of various mitogen-activated protein kinase inhibitors highlighted the role of p38, extracellular signal-regulated kinase, and c-Jun N-terminal kinase kinases in the observed effect. When BMSCs were pretreated with either histamine or degranulated human mast cells, they exhibited an enhanced IL-6-dependent antiapoptotic effect on neutrophil granulocytes. Based on these observations, it is likely that introduction of BMSCs into a histamine-rich environment (such as any allergic setting) or pretreatment of these cells with synthetic histamine could have a significant modulatory effect on the therapeutic potential of BMSCs.<br /> (Copyright © 2011 AlphaMed Press.)
- Subjects :
- Animals
Apoptosis
Bone Marrow Cells physiology
Cells, Cultured
Coculture Techniques
Gene Expression
Granulocytes metabolism
Histamine pharmacology
Humans
Interleukin-6 metabolism
Interleukin-8 metabolism
MAP Kinase Signaling System
Male
Mast Cells metabolism
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Receptors, Histamine genetics
Receptors, Histamine metabolism
Stromal Cells physiology
Bone Marrow Cells metabolism
Histamine physiology
Receptors, Histamine physiology
Stromal Cells metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1549-4918
- Volume :
- 30
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Stem cells (Dayton, Ohio)
- Publication Type :
- Academic Journal
- Accession number :
- 22045589
- Full Text :
- https://doi.org/10.1002/stem.771