Watson M L, Grix S P, Jordan N J, Place G A, Dodd S, Leithead J, Poll C T, Yoshimura T, Westwick J
Department of Pharmacy and Pharmacology, University of Bath, UK.
Cytokine. 1998 May;10(5):346-52. doi: 10.1006/cyto.1997.0350.
Leukocyte accumulation and activation are key events in the pathogenesis of inflammatory lung disease. The ability of human airway smooth muscle cells (HASM) to contribute to the inflammatory process by its ability to produce the chemokines interleukin (IL) 8, monocyte chemotactic protein (MCP-1) and regulated on activation, normal T cell expressed and secreted (RANTES) was investigated. Cultured HASM, when stimulated with the pro-inflammatory cytokines IL-1 alpha (0.01-1 ng/ml) or tumour necrosis factor alpha (TNF-alpha, 0.3-30 ng/ml), synthesize and release substantial amounts of IL-8, as assessed by specific immunoassay, bioasssay (elevation of intracellular free calcium in human neutrophils), and upregulation of mRNA. These stimuli also increased MCP-1 production and mRNA expression, but RANTES mRNA expression was not detected at 24 h. The smooth muscle spasmogen endothelin 1 (1 microM) was unable to stimulate IL-8 or MCP-1 release or mRNA expression. These data indicate that HASM may constitute an important source of leukocyte attractants in the inflamed lung, where the inducing stimuli, IL-1 alpha and TNF-alpha, are also likely to be present.
白细胞的积聚和激活是炎症性肺病发病机制中的关键事件。研究了人气道平滑肌细胞（HASM）通过产生趋化因子白细胞介素（IL）-8、单核细胞趋化蛋白（MCP-1）以及受激活调节的正常T细胞表达和分泌因子（RANTES）来促进炎症过程的能力。通过特异性免疫测定、生物测定（人中性粒细胞内游离钙升高）和mRNA上调评估，培养的HASM在用促炎细胞因子IL-1α（0.01 - 1 ng/ml）或肿瘤坏死因子α（TNF-α，0.3 - 30 ng/ml）刺激时，会合成并释放大量的IL-8。这些刺激也增加了MCP-1的产生和mRNA表达，但在24小时时未检测到RANTES mRNA表达。平滑肌收缩剂内皮素-1（1 μM）不能刺激IL-8或MCP-1的释放或mRNA表达。这些数据表明，HASM可能是炎症肺中白细胞趋化因子的重要来源，而炎症肺中也可能存在诱导刺激物IL-1α和TNF-α。
