Hayashi R, Yamashita N, Matsui S, Maruyama M, Sugiyama E, Sugiyama S, Kobayashi M
First Department of Internal Medicine, Toyama Medical, Toyama, Japan.
Immunology. 1998 Dec;95(4):507-11. doi: 10.1046/j.1365-2567.1998.00649.x.
Bradykinin (BK) is a potent inflammatory mediator that is generated from kininogens by the actions of plasma and tissue kallikreins. Lung fibroblasts have the potential to participate in the inflammatory responses by releasing proinflammatory cytokines in response to a variety of stimuli. We postulated that human lung fibroblasts might produce interleukin-8 (IL-8) in response to BK stimulation. The present study showed that BK stimulated human lung fibroblasts to produce IL-8 in a dose- and time-dependent manner. Furthermore, Northern blot analysis showed that BK increased IL-8 mRNA expression. The stimulatory effect of BK on IL-8 production was detected at the concentration of 10 nm, and the maximal stimulation was achieved with 100 to 1000 nm. Phorbol 12-myristate 13-acetate pretreatment diminished the ability of BK to stimulate IL-8 production. In addition, GF109203X, a selective protein kinase C inhibitor, blocked BK-induced IL-8 production. These observations suggest that the stimulatory effect of BK on IL-8 production by lung fibroblasts is, at least partially, mediated through protein kinase C. These data suggest that BK may be involved in the inflammatory reaction leading to interstitial lung disorders through stimulating IL-8 production by lung fibroblasts.
缓激肽（BK）是一种强效炎症介质，由血浆和组织激肽释放酶作用于激肽原产生。肺成纤维细胞有可能通过在多种刺激下释放促炎细胞因子来参与炎症反应。我们推测人肺成纤维细胞可能会在BK刺激下产生白细胞介素-8（IL-8）。本研究表明，BK以剂量和时间依赖性方式刺激人肺成纤维细胞产生IL-8。此外，Northern印迹分析显示BK增加了IL-8 mRNA的表达。在10 nM的浓度下检测到BK对IL-8产生的刺激作用，在100至1000 nM时达到最大刺激。佛波醇12-肉豆蔻酸酯13-乙酸酯预处理降低了BK刺激IL-8产生的能力。此外，选择性蛋白激酶C抑制剂GF109203X阻断了BK诱导的IL-8产生。这些观察结果表明，BK对肺成纤维细胞产生IL-8的刺激作用至少部分是通过蛋白激酶C介导的。这些数据表明，BK可能通过刺激肺成纤维细胞产生IL-8而参与导致间质性肺病的炎症反应。
