The histamine H4 receptor regulates chemokine production in human natural killer cells.
BACKGROUND
Natural killer (NK) cells have been detected in the lesional skin of patients with inflammatory skin diseases, where high levels of histamine are also present. Therefore, we investigated the effect of histamine, in particular via the histamine H4 receptor (H4R), on gene expression levels in human NK cells.


METHODS
Comprehensive microarray-based mRNA expression profiling was performed to assess the gene expression levels in human NK cells in response to H4R stimulation in an unbiased approach. The expression of selected cytokines and chemokines was quantified by real-time PCR and enzyme-linked immunosorbent assay.


RESULTS
The microarray analysis identified only few genes which were differentially regulated upon H4R stimulation. In follow-up studies, a significant upregulation of CCL3 and CCL4 at the mRNA level and in addition for CCL3 also at the protein level via the H4R was observed.


CONCLUSIONS
The elevated expression levels of chemokines in response to H4R stimulation might foster the inflammation in allergic skin diseases and characterize the H4R as a promising therapeutic target.
Department of Dermatology and Allergy, Division of Immunodermatology and Allergy Research, Hannover Medical School, Hannover, Germany.
Susanne
S
Mommert
Oliver
O
Dittrich-Breiholz
Holger
H
Stark
Ralf
R
Gutzmer
Thomas
T
Werfel
D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D054405:Chemokine CCL3 / Q000096:biosynthesis; D054407:Chemokine CCL4 / Q000096:biosynthesis; D016207:Cytokines / Q000096:biosynthesis*; D003876:Dermatitis, Atopic / Q000276:immunology*; D006801:Humans; D007249:Inflammation / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology*; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000235:genetics; D043562:Receptors, G-Protein-Coupled / Q000276:immunology*; D011968:Receptors, Histamine / Q000276:immunology*; D000074040:Receptors, Histamine H4
C515429:CCL3 protein, human; C066507:CCL4 protein, human; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D016207:Cytokines; C418607:HRH4 protein, human; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; D011968:Receptors, Histamine; D000074040:Receptors, Histamine H4