Abstract
Background: Histamine is an important mediator of allergic diseases. It modulates the cytokine expression of various subtypes of antigen-presenting cells by four known receptors, H<sub>1</sub>R-H<sub>4</sub>R. The effects of histamine on myeloid dendritic cells (mDC) are unclear. Methods: Monocytes and mDC were isolated from human PBMC. Histamine receptor expression was evaluated by real-time PCR. Cells were stimulated with histamine and histamine receptor ligands, and restimulated with polyinosinic-polycytidylic acid (poly I:C), and supernatants were analyzed by protein array and ELISA. Results: Monocytes and mDC express H<sub>1</sub>R and H<sub>2</sub>R without significant differences between the two cell types, whereas H<sub>4</sub>R mRNA was significantly higher in mDC compared with monocytes and H<sub>3</sub>R mRNA was not detected in any cell type. Prestimulation with histamine caused a significant decrease in poly I:C-induced expression of interferon-γ-induced protein (IP-10) in mDC and monocytes. Stimulation with specific H<sub>1</sub>R, H<sub>2</sub>R and H<sub>4</sub>R agonists and antagonists showed that the observed effect was mediated via H<sub>2</sub>R and H<sub>4</sub>R in monocytes and mDC. Conclusion: Monocytes and mDC have similar histamine receptor repertoires with regard to H<sub>1</sub>R, H<sub>2</sub>R and H<sub>3</sub>R, but H<sub>4</sub>R expression is higher on mDC. Histamine stimulation shows similar functional effects on both cell types, i.e., downregulation of TLR3-induced IP-10 production. This might be a new mechanism how histamine fosters a Th2 milieu.
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