Pavlinkova Gabriela, Yanagawa Yoshiki, Kikuchi Kazuhiro, Iwabuchi Kazuya, Onoé Kazunori
Division of Immunobiology, Institute for Genetic Medicine, Hokkaido University, Sapporo, Japan.
Immunobiology. 2003;207(5):315-25. doi: 10.1078/0171-2985-00247.
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.
越来越多的证据表明，组胺会影响树突状细胞（DC）的激活、成熟以及Th1/Th2分化偏好。在本文中，我们报告组胺会影响源自小鼠脾脏的未成熟DC（iDC）系中白细胞介素（IL）-12和IL-6的产生。与未用组胺处理的iDC相比，用组胺处理iDC可显著提高IL-12 p40的mRNA和蛋白水平。在存在肿瘤坏死因子（TNF）-α的情况下，组胺也会增加IL-12 p40和IL-6的产生。然而，组胺会以浓度依赖的方式显著降低脂多糖（LPS）刺激的DC产生的IL-12 p40。当通过RT-PCR分析DC中组胺H1（H1R）和H2（H2R）受体的表达时，与未刺激的iDC相比，LPS或TNF-α刺激后这两种受体均下调。组胺处理可显著增加iDC中H2R mRNA的表达以及LPS激活的DC中H1R mRNA的表达。然而，组胺处理会降低TNF-α刺激的DC中两种组胺受体的表达。使用异硫氰酸荧光素（FITC）偶联的组胺进行流式细胞术分析也得到了类似结果。这些结果表明，组胺可调节其自身受体的表达并激活iDC，这可能以成熟信号依赖的方式影响成熟DC的后续功能状态。因此，组胺可能会影响免疫反应结果。
