Tasaka K, Mio M, Shimazawa M, Nakaya N
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Okayama University, Japan.
Mol Pharmacol. 1993 Mar;43(3):365-71.
In this study, the role of histamine in interleukin-1 (IL-1) formation in murine bone marrow stromal cells was investigated in vitro. It was found that histamine and 4-methylhistamine increased the number of granulocyte colony-forming units in murine bone marrow cells. A similar effect was elicited by dibutyryl-cAMP and theophylline. When histamine and H2 agonists, such as 4-methylhistamine and dimaprit, were added to the culture medium containing murine bone marrow stromal cells, thymocyte comitogenic activity detected in the medium increased significantly. However, no such effect was observed in the case of 2-methyl-histamine, an H1 agonist. Histamine-induced production of thymocyte comitogenic activity in bone marrow stromal cells was inhibited by some H2 antagonists, such as cimetidine, ranitidine, and famotidine, but not by the H1 antagonist pyrilamine. Histamine was also effective in inducing the colony-promoting activity in murine bone marrow stromal cells. This was also inhibited by H2 antagonists such as cimetidine, ranitidine, and famotidine. Histamine elicited an increase in cAMP content in bone marrow stromal cells. From gel filtration analysis, the molecular mass of the active substance produced by bone marrow stromal cells in response to histamine was in the range of 15 to 20 kDa. By means of Western blotting analysis, it was found that production of pro-IL-1 alpha in the bone marrow stromal cells was induced by histamine. The production of pro-IL-1 alpha in bone marrow stromal cells stimulated by histamine was inhibited not only by H2 antagonists, such as cimetidine, ranitidine, and famotidine, but also by the protein kinase A antagonist KT-5720. These results indicate that histamine stimulates the production of IL-1 alpha in bone marrow stromal cells and that this results in the proliferation and differentiation of neutrophil progenitor cells.
在本研究中，体外研究了组胺在小鼠骨髓基质细胞白细胞介素-1（IL-1）形成中的作用。发现组胺和4-甲基组胺增加了小鼠骨髓细胞中粒细胞集落形成单位的数量。二丁酰环磷腺苷和茶碱也产生了类似的效果。当将组胺和H2激动剂（如4-甲基组胺和二甲双胍）添加到含有小鼠骨髓基质细胞的培养基中时，培养基中检测到的胸腺细胞促有丝分裂活性显著增加。然而，H1激动剂2-甲基组胺则未观察到这种效果。骨髓基质细胞中组胺诱导的胸腺细胞促有丝分裂活性的产生受到一些H2拮抗剂（如西咪替丁、雷尼替丁和法莫替丁）的抑制，但不受H1拮抗剂吡苄明的抑制。组胺在诱导小鼠骨髓基质细胞的集落促进活性方面也有效。这也受到西咪替丁、雷尼替丁和法莫替丁等H2拮抗剂的抑制。组胺引起骨髓基质细胞中cAMP含量增加。通过凝胶过滤分析，骨髓基质细胞响应组胺产生的活性物质的分子量在15至20 kDa范围内。通过蛋白质印迹分析发现，组胺诱导骨髓基质细胞中前IL-1α的产生。组胺刺激的骨髓基质细胞中前IL-1α的产生不仅受到西咪替丁、雷尼替丁和法莫替丁等H2拮抗剂的抑制，还受到蛋白激酶A拮抗剂KT-57二零龙的抑制。这些结果表明，组胺刺激骨髓基质细胞中IL-1α的产生，这导致中性粒细胞祖细胞的增殖和分化。
