Xie Guogang, Wang Feng, Peng Xia, Liang Yuting, Yang Haiwei, Li Li
Department of Respiratory Medicine, Shanghai General Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China.
Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Cell Physiol Biochem. 2018;46(6):2401-2411. doi: 10.1159/000489646. Epub 2018 May 4.
BACKGROUND/AIMS: As a major inflammatory molecule released from mast cell activation, histamine has been reported to regulate TLRs expression and cytokine production in inflammatory cells present in the microenvironment. In this study, we determined the ability of histamine to modulate TLRs expression and cytokine production in mast cells.
HMC-1 and P815 cells were exposed to various concentrations of histamine in the presence or absence of histamine antagonist for 2, 6 or 16 h. The effect of histamine on the expression of TLR3 protein and mRNA was analyzed by flow cytometry、 RT-PCR and immunofluorescent microscopy. Furthermore, we also examined the effect of histamine on the secretion of MCP-1 and IL-13 from mast cells by ELISA.
The amplification of TLR3 mRNA and protein expression in mast cells was observed after incubation with histamine, which was accompanied by increasing secretion of IL-13 and MCP-1 via H1 receptor. The signaling pathways of PI3K/ Akt and Erk1/2/MAPK contributed to these induction effects.
These results demonstrate that histamine up-regulates the expression of TLR3 and secretion of IL-13 and MCP-1 in mast cells, thus identifying a new mechanism for the histamine inducing allergic response.
背景/目的：作为肥大细胞激活后释放的主要炎症分子，据报道组胺可调节微环境中炎症细胞内Toll样受体（TLRs）的表达及细胞因子的产生。在本研究中，我们测定了组胺调节肥大细胞中TLRs表达及细胞因子产生的能力。
将HMC-1和P815细胞在存在或不存在组胺拮抗剂的情况下，暴露于不同浓度的组胺中2、6或16小时。通过流式细胞术、逆转录-聚合酶链反应（RT-PCR）和免疫荧光显微镜分析组胺对TLR3蛋白和mRNA表达的影响。此外，我们还通过酶联免疫吸附测定（ELISA）检测了组胺对肥大细胞分泌单核细胞趋化蛋白-1（MCP-1）和白细胞介素-13（IL-13）的影响。
与组胺孵育后，观察到肥大细胞中TLR3 mRNA和蛋白表达增加，同时通过H1受体导致IL-13和MCP-1分泌增加。磷脂酰肌醇-3激酶（PI3K）/蛋白激酶B（Akt）和细胞外信号调节激酶1/2（Erk1/2）/丝裂原活化蛋白激酶（MAPK）信号通路促成了这些诱导作用。
这些结果表明，组胺上调肥大细胞中TLR3的表达以及IL-13和MCP-1的分泌，从而确定了组胺诱导过敏反应的新机制。
