Effects of histamine on functional maturation of dendritic cells.
There is increasing evidence that histamine affects dendritic cell (DC) activation, maturation, and preference for Th1/Th2 differentiation. In this paper we report that histamine affects interleukin (IL)-12 and IL-6 production in an immature DC (iDC) line derived from murine spleen. Histamine treatment of iDC significantly increased the IL-12 p40 mRNA and protein levels compared to histamine untreated iDC. In the presence of tumor necrosis factor (TNF)-alpha histamine also increased IL-12 p40 and IL-6 production. However, histamine significantly decreased IL-12 p40 production by lipopolysaccharide (LPS)-stimulated DC in a concentration dependent manner. When expressions of histamine H1 (H1R) and H2 (H2R) receptors in DC were analyzed by RT-PCR, both receptors were down-regulated after LPS or TNF-alpha stimulation compared to unstimulated iDC. Histamine treatment significantly increased the expression of H2R mRNA in iDC and H1R mRNA in LPS-activated DC. However, histamine treatment decreased the expression of both histamine receptors in TNF-alpha-stimulated DC. Similar results were obtained by flow cytometry with FITC-conjugated histamine. These results demonstrate that histamine can regulate the expression of its own receptors and activate iDC, which may influence subsequent functional states of mature DC in a maturation signal-dependent manner. Consequently, histamine may contribute to an immune response outcome.
Pavlinkova
Gabriela
G
Division of Immunobiology, Institute for Genetic Medicine, Hokkaido University, Sapporo, Japan.
Yanagawa
Yoshiki
Y
Kikuchi
Kazuhiro
K
Iwabuchi
Kazuya
K
Onoé
Kazunori
K
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D051940:B7-2 Antigen; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D005434:Flow Cytometry; D006632:Histamine / Q000494:pharmacology*; D006633:Histamine Antagonists / Q000494:pharmacology; D018664:Interleukin-12 / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D010641:Phenotype; D011968:Receptors, Histamine / Q000235:genetics / Q000378:metabolism; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D015703:Antigens, CD; D051940:B7-2 Antigen; C497965:Cd86 protein, mouse; D006633:Histamine Antagonists; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D011968:Receptors, Histamine; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12; D006632:Histamine