Characterization and function of histamine receptors in human bone marrow stromal cells

Krisztian Nemeth, Todd Wilson, Balazs Rada, Alissa Parmelee, Balazs Mayer, E. Búzás, A. Falus, Sharon Key, T. Masszi, S. Kárpáti, Eva Mezey

Research output: Contribution to journalArticle

19 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)222-231
Number of pages10
JournalStem Cells
Volume30
Issue number2
DOIs
Publication statusPublished - Feb 2012

Fingerprint

Histamine Receptors
Mesenchymal Stromal Cells
Histamine
Interleukin-6
Artificial Cells
Histamine H1 Receptors
Histamine H2 Receptors
JNK Mitogen-Activated Protein Kinases
Immune System Diseases
Extracellular Signal-Regulated MAP Kinases
Therapeutic Uses
Protein Kinase Inhibitors
Mitogen-Activated Protein Kinases
Granulocytes
Mast Cells
Neutrophils
Phosphotransferases
Western Blotting
Clinical Trials

Keywords

  • Adult stem cells
  • Apoptosis
  • Bone marrow stromal cells
  • IL-6R/IL-6
  • Mesenchymal stem cells

ASJC Scopus subject areas

  • Cell Biology
  • Developmental Biology
  • Molecular Medicine

Cite this

Nemeth, K., Wilson, T., Rada, B., Parmelee, A., Mayer, B., Búzás, E., ... Mezey, E. (2012). Characterization and function of histamine receptors in human bone marrow stromal cells. Stem Cells, 30(2), 222-231. https://doi.org/10.1002/stem.771

Characterization and function of histamine receptors in human bone marrow stromal cells. / Nemeth, Krisztian; Wilson, Todd; Rada, Balazs; Parmelee, Alissa; Mayer, Balazs; Búzás, E.; Falus, A.; Key, Sharon; Masszi, T.; Kárpáti, S.; Mezey, Eva.

In: Stem Cells, Vol. 30, No. 2, 02.2012, p. 222-231.

Research output: Contribution to journalArticle

Nemeth, Krisztian ; Wilson, Todd ; Rada, Balazs ; Parmelee, Alissa ; Mayer, Balazs ; Búzás, E. ; Falus, A. ; Key, Sharon ; Masszi, T. ; Kárpáti, S. ; Mezey, Eva. / Characterization and function of histamine receptors in human bone marrow stromal cells. In: Stem Cells. 2012 ; Vol. 30, No. 2. pp. 222-231.
@article{81917c8482a04983a628160ffb8fedb6,
title = "Characterization and function of histamine receptors in human bone marrow stromal cells",
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.",
keywords = "Adult stem cells, Apoptosis, Bone marrow stromal cells, IL-6R/IL-6, Mesenchymal stem cells",
author = "Krisztian Nemeth and Todd Wilson and Balazs Rada and Alissa Parmelee and Balazs Mayer and E. B{\'u}z{\'a}s and A. Falus and Sharon Key and T. Masszi and S. K{\'a}rp{\'a}ti and Eva Mezey",
year = "2012",
month = "2",
doi = "10.1002/stem.771",
language = "English",
volume = "30",
pages = "222--231",
journal = "Stem Cells",
issn = "1066-5099",
publisher = "AlphaMed Press",
number = "2",

}

TY - JOUR

T1 - Characterization and function of histamine receptors in human bone marrow stromal cells

AU - Nemeth, Krisztian

AU - Wilson, Todd

AU - Rada, Balazs

AU - Parmelee, Alissa

AU - Mayer, Balazs

AU - Búzás, E.

AU - Falus, A.

AU - Key, Sharon

AU - Masszi, T.

AU - Kárpáti, S.

AU - Mezey, Eva

PY - 2012/2

Y1 - 2012/2

N2 - 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.

AB - 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.

KW - Adult stem cells

KW - Apoptosis

KW - Bone marrow stromal cells

KW - IL-6R/IL-6

KW - Mesenchymal stem cells

UR - http://www.scopus.com/inward/record.url?scp=84856082907&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84856082907&partnerID=8YFLogxK

U2 - 10.1002/stem.771

DO - 10.1002/stem.771

M3 - Article

C2 - 22045589

AN - SCOPUS:84856082907

VL - 30

SP - 222

EP - 231

JO - Stem Cells

JF - Stem Cells

SN - 1066-5099

IS - 2

ER -