Knight D A, Lydell C P, Zhou D, Weir T D, Robert Schellenberg R, Bai T R
University of British Columbia Pulmonary Research Laboratory, St. Paul's Hospital, Vancouver, British Columbia, Canada.
Am J Respir Cell Mol Biol. 1999 Apr;20(4):834-41. doi: 10.1165/ajrcmb.20.4.3429.
The distribution and regulation of leukemia inhibitory factor (LIF) and its receptor (LIFR) in human lung tissue is unknown. We recently found that LIF was immunolocalized to several cell types in human airways, and that exogenous LIF modulated neural and contractile responses of explanted airways. The present study aimed to determine the cellular distribution and regulation of gene transcripts for LIF and LIFR in human lung, and measured the release of LIF in response to anti-immunoglobulin (Ig)E, interleukin (IL)-1beta, and IL-6. Exposure of human lung to IL-1beta (100 pg/ml) resulted in the rapid induction of LIF messenger RNA (mRNA) (1 h) and subsequent protein release (6 h). Similar results were observed when lung tissue was exposed to anti-IgE (6 U/ml). Gene transcripts for LIF were observed in nine pulmonary cell types, with the greatest expression occurring in fibroblasts. LIFR transcripts were also widely expressed in these cell types. In cultures of nontransformed epithelial cells, lung fibroblasts, and airway smooth-muscle cells, IL-1beta (100 pg/ml) induced the rapid accumulation of LIF mRNA and protein release, with fibroblasts liberating the greatest amount. IL-6 also induced the expression of LIF mRNA and release of LIF in airway smooth-muscle cells, whereas exogenous LIF itself had no effect. Expression of LIFR mRNA was not influenced by exposure to IL-1beta or LIF in any of the cell lines used. These results highlight the widespread distribution and rapid release of LIF in human lung tissue and, in conjunction with our previous report, suggest that this cytokine may play an important role in lung inflammatory processes and neuroimmune interactions.
白血病抑制因子（LIF）及其受体（LIFR）在人肺组织中的分布和调控尚不清楚。我们最近发现，LIF在人呼吸道的几种细胞类型中呈免疫定位，并且外源性LIF可调节离体呼吸道的神经和收缩反应。本研究旨在确定LIF和LIFR基因转录本在人肺中的细胞分布和调控，并测量LIF对抗免疫球蛋白（Ig）E、白细胞介素（IL）-1β和IL-6的释放反应。将人肺暴露于IL-1β（100 pg/ml）会导致LIF信使核糖核酸（mRNA）迅速诱导（1小时），随后蛋白质释放（6小时）。当肺组织暴露于抗IgE（6 U/ml）时，观察到了类似结果。在九种肺细胞类型中观察到了LIF的基因转录本，其中成纤维细胞中的表达最为显著。LIFR转录本在这些细胞类型中也广泛表达。在未转化的上皮细胞、肺成纤维细胞和气道平滑肌细胞培养物中，IL-1β（100 pg/ml）诱导LIF mRNA迅速积累和蛋白质释放，成纤维细胞释放的量最大。IL-6也诱导气道平滑肌细胞中LIF mRNA的表达和LIF的释放，而外源性LIF本身没有影响。在所使用的任何细胞系中，暴露于IL-1β或LIF均不影响LIFR mRNA的表达。这些结果突出了LIF在人肺组织中的广泛分布和快速释放，并且结合我们之前的报告表明，这种细胞因子可能在肺部炎症过程和神经免疫相互作用中发挥重要作用。
