Histamine and Histamine H4 Receptor Promotes Osteoclastogenesis in Rheumatoid Arthritis.
Histamine and Histamine H4 Receptor Promotes Osteoclastogenesis in Rheumatoid Arthritis.
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DOI：
10.1038/s41598-017-01101-y
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发表时间：
2017-04-26
影响因子：
4.6
通讯作者：
Kim HR
中科院分区：
文献类型：
--
作者：
Kim KW;Kim BM;Lee KA;Lee SH;Firestein GS;Kim HR
组胺H4受体（H4 R）在多种免疫细胞中具有免疫调节和趋化作用。本研究的目的是确定破骨细胞的作用H4 R类风湿关节炎（RA）。用ELISA法测定RA患者关节液和血清中组胺浓度。用组胺、IL-17、IL-21、IL-22和H4 R拮抗剂（JNJ 7777120）处理RA SF和外周血（PB）CD 14+单核细胞后，用实时荧光定量PCR检测H4 R和RANKL基因表达。通过计数与组胺、Th 17细胞因子和JNJ 7777120一起培养的PB CD 14+单核细胞中的TRAP阳性多核细胞来评估破骨细胞生成。RA组SF和血清组胺浓度高于骨关节炎组和健康对照组。RA患者外周血单核细胞H4 R表达增加。组胺、IL-6、IL-17、IL-21和IL-22诱导单核细胞H4 R的表达。组胺、IL-17和IL-22刺激RA单核细胞中的RANKL表达，JNJ 7777120降低RANKL表达。组胺和Th 17细胞因子诱导单核细胞向破骨细胞分化，JNJ 7777120抑制破骨细胞的分化。H4 R介导组胺和Th 17细胞因子诱导的RANKL表达和破骨细胞分化阻断H4 R可能成为预防RA骨质破坏的一种新的治疗方法。
Histamine H4 receptor (H4R) has immune-modulatory and chemotaxic effects in various immune cells. This study aimed to determine the osteoclastogenic role of H4R in rheumatoid arthritis (RA). The concentration of histamine in synovial fluid (SF) and sera in patients with RA was measured using ELISA. After RA SF and peripheral blood (PB) CD14+ monocytes were treated with histamine, IL-17, IL-21 and IL-22, and a H4R antagonist (JNJ7777120), the gene expression H4R and RANKL was determined by real-time PCR. Osteoclastogenesis was assessed by counting TRAP–positive multinucleated cells in PB CD14+ monocytes cultured with histamine, Th17 cytokines and JNJ7777120. SF and serum concentration of histamine was higher in RA, compared with osteoarthritis and healthy controls. The expression of H4R was increased in PB monocytes in RA patients. Histamine, IL-6, IL-17, IL-21 and IL-22 induced the expression of H4R in monocytes. Histamine, IL-17, and IL-22 stimulated RANKL expression in RA monocytes and JNJ7777120 reduced the RANKL expression. Histamine and Th17 cytokines induced the osteoclast differentiation from monocytes and JNJ7777120 decreased the osteoclastogenesis. H4R mediates RANKL expression and osteoclast differentiation induced by histamine and Th17 cytokines. The blockage of H4R could be a new therapeutic modality for prevention of bone destruction in RA.