Inhibition of GM-CSF production in fibroblast-monocyte coculture by prednisone and effects of RHGM-CSF on human lung fibroblasts
Inhibition of GM-CSF production in fibroblast-monocyte coculture by prednisone and effects of RHGM-CSF on human lung fibroblasts
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DOI：
10.2741/1240
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发表时间：
2004-01-01
期刊：
影响因子：
--
通讯作者：
Krishnaswamy, G
中科院分区：
文献类型：
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作者：
Fitzgerald, SM;Chi, DS;Krishnaswamy, G
成纤维细胞在哮喘疾病中起着前哨作用。它们是结缔组织的主要成分，在哮喘肺中数量增加。它们还能够分泌多种细胞因子，并且能够被促炎细胞因子和细胞-细胞接触激活。以前我们曾报道过正常人肺成纤维细胞（NHLF）可以被单核细胞（U937）通过细胞-细胞接触激活产生GM-CSF。在这里，我们表明，由单核细胞接触激活的NHLF产生GM-CSF被泼尼松（一种用于治疗哮喘的合成糖皮质激素）抑制。GM-CSF是一种酸性糖蛋白，可促进粒细胞和巨噬细胞谱系中细胞的发育，并在外周炎症部位分泌。通过流式细胞术在NHLF上发现了GM-CSF受体，并且能够被白细胞介素（IL）-1 β、肿瘤坏死因子（TNF）α和重组人（rh）GM-CSF上调。为了测试GM-CSF对成纤维细胞的自分泌作用，在增殖研究中使用rh GM-CSF，发现其降低成纤维细胞增殖。强的松也用于阻断NF-κ B活化和GM-CSF基因表达。这些数据表明细胞-细胞接触介导的具有成纤维细胞的浸润单核细胞的炎症的作用机制和治疗，如在哮喘和其他疾病如移植物抗宿主病中所见。
Fibroblasts play a sentinel role in asthmatic disease. They are the main constituents of connective tissue and are increased in number in the asthmatic lung. They are also capable of secreting a diverse repertoire of cytokines and are able to be activated by pro-inflammatory cytokines and cell-cell contact. Previously we have reported that normal human lung fibroblasts (NHLF) can be activated by monocytes (U937) through cell-cell contact to produce GM-CSF. Here we show that GM-CSF production from NHLF activated by monocyte contact is inhibited by prednisone, a synthetic glucocorticoid used in the treatment of asthma. GM-CSF is an acidic glycoprotein that potentiates development of cells in the granulocyte and macrophage lineage and is secreted at sites of peripheral inflammation. The receptor for GM-CSF was found on NHLF by flow cytometry and was able to be up-regulated by interleukin (IL)-1 beta, tumor necrosis factor (TNF)alpha and recombinant human ( rh) GM-CSF. To test autocrine effects of GM-CSF on fibroblasts, rh GM-CSF was used in proliferation studies and was found to decrease fibroblast proliferation. Prednisone was used to block NF-kappaB activation and GM-CSF gene expression as well. These data indicate mechanism of action and treatment for cell-cell contact mediated inflammation of infiltrating monocytes with fibroblasts as seen in asthma and other diseases like graft versus host disease.