Brief Report: First identification of H4 histamine receptor in healthy salivary glands and in focal sialadenitis in Sjogren's syndrome
Brief Report: First identification of H4 histamine receptor in healthy salivary glands and in focal sialadenitis in Sjogren's syndrome
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DOI：
10.1002/art.34484
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发表时间：
2012-08-01
影响因子：
--
通讯作者：
Konttinen, Y. T.
中科院分区：
文献类型：
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作者：
Stegaev, V.;Sillat, T.;Konttinen, Y. T.
目的常规H1和H2组胺受体对组胺的亲和力比H4组胺受体低10万倍，与自身免疫性疾病有关。本研究旨在比较健康对照者和原发性干燥综合征（SS）患者唾液腺（SGs）中H4组胺受体的水平。方法采用实时定量聚合酶链反应法检测H4组胺受体信使RNA (mRNA)，免疫染色法检测受体蛋白。采用xMAP技术和酶联免疫吸附法分析H4组胺受体激动剂ST-1006对人SG （HSG）细胞合成细胞因子的影响。结果健康SGs中含有H4组胺受体mRNA。受体蛋白定位于腺泡上皮细胞和导管上皮细胞。H4组胺受体激动剂刺激HSG细胞产生白细胞介素-8和血管内皮生长因子。SS患者H4组胺受体水平低。结论H1和H2组胺受体拮抗剂治疗自身免疫性疾病无效。然而，这些拮抗剂不影响新发现的H4组胺受体。树突状细胞和淋巴细胞是非专业的产生组胺的细胞，它们产生组胺的速度比肥大细胞低1001 000倍。唾液中只含有0.3112.4 ng/ml的组胺，这一含量过低，不能刺激H1或H2组胺受体，但能最大程度地刺激H4组胺受体的一半。我们的研究结果表明，H4组胺受体在小管腺泡SG细胞中强烈表达，这强调了这些细胞在SS发病中的作用。
Objective The conventional H1 and H2 histamine receptors have >10,000-fold lower avidity for histamine than H4 histamine receptor, which has been implicated in autoimmune diseases. This study was undertaken to compare H4 histamine receptor levels in the salivary glands (SGs) of healthy controls with those in the SGs of patients with primary Sjogren's syndrome (SS). Methods H4 histamine receptor messenger RNA (mRNA) was analyzed using real-time quantitative polymerase chain reaction, and the receptor protein was examined using immunostaining. Effects of the H4 histamine receptor agonist ST-1006 on cytokine synthesis by human SG (HSG) cells were analyzed using xMAP technology and enzyme-linked immunosorbent assay. Results Healthy SGs contained H4 histamine receptor mRNA. The receptor protein was localized to the acinar and ductal epithelial cells. H4 histamine receptor agonist stimulated HSG cells to produce the cytokines interleukin-8 and vascular endothelial growth factor. SS patients had low H4 histamine receptor levels. Conclusion H1 and H2 histamine receptor antagonists are not effective in the treatment of autoimmune diseases. However, such antagonists do not affect the newly discovered H4 histamine receptor. Dendritic cells and lymphocytes are nonprofessional histamine-producing cells, which produce histamine at 1001,000-fold lower rates than mast cells do. Saliva contains only 0.3112.4 ng/ml histamine, which is too low to stimulate H1 or H2 histamine receptor, but stimulates H4 histamine receptor half maximally. Our findings show that H4 histamine receptor is strongly expressed in tubuloacinar SG cells, which emphasizes the role of these cells in the pathogenesis of SS.