Okayama Y, Okumura S, Sagara H, Yuki K, Sasaki T, Watanabe N, Fueki M, Sugiyama K, Takeda K, Fukuda T, Saito H, Ra C
Division of Molecular Cell Immunology and Allergology, Advanced Medical Research Center, Nihon University Graduate School of Medical Science, Tokyo, Japan.
Eur Respir J. 2009 Aug;34(2):425-35. doi: 10.1183/09031936.00121008. Epub 2009 Jan 22.
A significant increase of mRNA expression of thymic stromal lymphopoietin (TSLP) has been reported in the bronchial mast cells (MCs) of asthmatic subjects; however, the mechanism underlying the upregulation of TSLP mRNA and protein remains unknown. FcepsilonRI-mediated activation of human MCs upregulated TSLP mRNA expression by 5.2+/-2.9-fold, while activation of the MCs using lipopolysaccharide and polyriboinosinic:polyribocytidylic acid failed to upregulate TSLP. Stimulation of MCs with interleukin (IL)-4 alone did not affect the TSLP mRNA expression, while pre-incubation of MCs with IL-4 for 48 h significantly enhanced the FcepsilonRI-mediated TSLP mRNA expression (by 53.7+/-15.9-fold; p<0.05) and the amount of TSLP in the cell pellets increased significantly from 23.4+/-4.3 pg mL(-1) to 121.5+/-3.7 pg mL(-1) (p<0.0001). However, the released TSLP was rapidly degraded by proteases that were released by MCs. We identified the population of cells expressing TSLP in the lungs of 16 asthmatic and 11 control subjects by immunohistochemistry. The percentage of TSLP-positive MCs in the total population of MCs was significantly increased in asthmatic airways (p<0.0001). Thus, MCs are able to store TSLP intracellularly and to produce TSLP following aggregation of FcepsilonRI in the presence of IL-4.
据报道，哮喘患者支气管肥大细胞（MCs）中胸腺基质淋巴细胞生成素（TSLP）的mRNA表达显著增加；然而，TSLP mRNA和蛋白上调的潜在机制仍不清楚。FcepsilonRI介导的人MCs激活使TSLP mRNA表达上调了5.2±2.9倍，而使用脂多糖和聚肌苷酸:聚胞苷酸激活MCs未能上调TSLP。单独用白细胞介素（IL）-4刺激MCs不影响TSLP mRNA表达，而MCs与IL-4预孵育48小时显著增强了FcepsilonRI介导的TSLP mRNA表达（上调53.7±15.9倍；p<0.05），细胞沉淀中TSLP的量从23.4±4.3 pg mL（-1）显著增加到121.5±3.7 pg mL（-1）（p<0.0001）。然而，释放的TSLP会被MCs释放的蛋白酶迅速降解。我们通过免疫组织化学鉴定了16名哮喘患者和11名对照受试者肺中表达TSLP的细胞群体。哮喘气道中TSLP阳性MCs在MCs总数中的百分比显著增加（p<0.0001）。因此，MCs能够在细胞内储存TSLP，并在IL-4存在下FcepsilonRI聚集后产生TSLP。
