Characterization and Function of Histamine Receptors in Human Bone Marrow Stromal Cells
| Autor: | Krisztián Németh, Todd M. Wilson, Balázs Rada, Alissa Parmelee, András Falus, Eva Mezey, Sharon Key, Sarolta Kárpáti, Balázs Mayer, Tamás Masszi, Edit I. Buzás |
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| Rok vydání: | 2012 |
| Předmět: |
Male
Stromal cell MAP Kinase Signaling System Gene Expression Apoptosis Bone Marrow Cells Pharmacology Biology Article Cell therapy Mice chemistry.chemical_compound Histamine receptor Immune system medicine Animals Humans Mast Cells Receptor Protein kinase A Cells Cultured Mice Inbred BALB C Interleukin-6 Interleukin-8 Cell Biology Coculture Techniques Mice Inbred C57BL medicine.anatomical_structure chemistry Immunology Receptors Histamine Molecular Medicine Bone marrow Stromal Cells Histamine Granulocytes Developmental Biology |
| Zdroj: | Stem Cells. 30:222-231 |
| ISSN: | 1549-4918 1066-5099 |
| DOI: | 10.1002/stem.771 |
| Popis: | 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. Disclosure of potential conflicts of interest is found at the end of this article. |
| Databáze: | OpenAIRE |
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