[Frontiers in Bioscience E3, 1414-1424, June 1, 2011]

Histamine regulates relevant murine dendritic cell functions via H4 receptor

Tunde Simon1,2, Valeria Laszlo2, Orsolya Lang2, Edit Buzas2, Andras Falus2,3

1Institute of Immunology, University of Debrecen, Debrecen, Hungary, 2Department of Genetics, Cell- and Immunobiology, Semmelweis University, Budapest, Hungary, 3Research Group for Inflammation Biology and Immunogenomics, Hungarian Academy of Sciences, Budapest, Hungary

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Materials and methods
3.1. Mice
3.2. Isolation of DCs from spleen
3.3. DC differentiation in bone marrow cultures
3.4. In vitro antigen presentation assay
3.5. Migration assay
3.6. Cell adhesion assay
3.7. In vitro DC stimulation
3.8. In vivo DC stimulation
3.9. Quantitative real-time PCR
3.10. Flow cytometry
3.11. Statistics
4. Results
4.1. Role of histamine and H4R in DC antigen presentation
4.2. Migration studies
4.3. Adhesion studies
4.4. Cytokine production of in vitro stimulated DCs
4.5. Cytokine responses of in vivo activated WT and H4R-/- DCs
5. Discussion
6. Acknowledgement
7. References

1. ABSTRACT

Histamine, produced by dendritic cells (DCs) or by other cells of the immune system, may have significant impact on DC activities. We investigated the influence of histamine and histamine H4 receptor (H4R) on some relevant functions of DCs. Histamine significantly decreased the antigen presentation capacity of splenic DCs, and this effect was reversed by a H4R antagonist. Furthermore, enhanced antigen presentation was detected in H4R-/- DCs. Prolonged histamine treatment during DC differentiation stimulated migration, albeit the increase was not significant. H4R-deficient DCs possessed significantly lower migration capacity than their wild-type counterparts. Monitoring in vivo and in vitro DC cytokine production revealed that a H4R agonist in combination with LPS, increased IL-1 beta mRNA expression, and a H4R antagonist reversed this effect. In H4R-deficient mice we detected decreased mRNA expression of some DC-derived cytokines including IFN-gamma and IL-10. Upon CFA stimulation, genotype-dependent differences were found in the expression of IL-6 and IFN-gamma. Our data suggest that H4R plays a crucial role in variety of functions of murine DCs.