PRODUCTION OF MACROPHAGE-COLONY-STIMULATING FACTOR (M-CSF) BY HUMAN ARTICULAR-CARTILAGE AND CHONDROCYTES - MODULATION BY INTERLEUKIN-1 AND TUMOR-NECROSIS-FACTOR-ALPHA
PRODUCTION OF MACROPHAGE-COLONY-STIMULATING FACTOR (M-CSF) BY HUMAN ARTICULAR-CARTILAGE AND CHONDROCYTES - MODULATION BY INTERLEUKIN-1 AND TUMOR-NECROSIS-FACTOR-ALPHA
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DOI：
10.1016/0925-4439(93)90153-r
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发表时间：
1993-08-04
期刊：
影响因子：
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通讯作者：
HAMILTON, JA
中科院分区：
文献类型：
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作者：
CAMPBELL, IK;IANCHES, G;HAMILTON, JA
用放射免疫法检测器官培养和细胞培养的人关节软骨和软骨细胞单层细胞产生巨噬细胞集落刺激因子(M-CSF)的能力。IL-1的最佳剂量为10~100U/ml(0.06~0.6 nM IL-1α；0.02~0.2 nM IL-1β)，TNFα的最佳剂量为1~10 nM。未经刺激的培养上清液中M-CSF水平较低，而IL-1α和TNFα作用2 h后，M-CSF水平升高。当IL-1α和TNFα同时加入培养物中时，两者对M-CSF的产生没有协同作用。放线菌素D和放线菌亚胺抑制基础和IL-1α诱导的M-CSF的产生，这表明需要从头合成RNA和蛋白质。细胞因子诱导的M-CSF的产生也被抗炎皮质类固醇地塞米松抑制，但不被环氧合酶抑制剂吲哚美辛抑制。细胞因子IL-4、IL-6、血小板衍生生长因子、白血病抑制因子、转化生长因子-β、干扰素-α和干扰素-α对M-CSF水平影响很小或无影响，而碱性成纤维细胞生长因子、脂多糖和维甲酸均为弱刺激。我们认为，软骨细胞对IL-1和TNFα的应答产生M-CSF，以及这些细胞因子对软骨的同时破坏，可能为类风湿疾病的慢性性质提供了一种机制。
A specific radioimmunoassay was employed to demonstrate that human articular cartilage and chondrocyte monolayers in organ and cell culture, respectively, produce macrophage colony-stimulating factor (M-CSF) in response to stimulation with interleukin-1alpha (IL-1alpha), IL-1beta, tumor necrosis factor alpha (TNFalpha) and TNFbeta. Optimum doses were 10-100 U/ml for IL-1 (0.06-0.6 nM IL-1alpha; 0.02-0.2 nM IL-1beta) and 1-10 nM for TNFalpha. Low levels of M-CSF were observed in the supernatants of nonstimulated cultures while increased levels of M-CSF in response to IL-1alpha and TNFalpha were detected following 2 h exposure to the cytokines. IL-1alpha and TNFalpha did not show synergy for the production of M-CSF when both cytokines were added to cultures. Actinomycin D and cycloheximide inhibited both the basal and IL-1alpha-induced production of M-CSF, suggesting a requirement for de novo RNA and protein synthesis. Cytokine-induced M-CSF production was also inhibited by the antiinflammatory corticosteroid, dexamethasone, but not by the cyclooxygenase inhibitor, indomethacin. The cytokines IL-4, IL-6, platelet-derived growth factor, leukemia inhibitory factor, transforming growth factor-beta and interferons -alpha and -gamma, each had little or no effect on M-CSF levels, while basic fibroblast growth factor, lipopolysaccharide, and retinoic acid were each weak stimuli. We propose that chondrocyte M-CSF production in response to IL-1 and TNFalpha, and the concurrent destruction of cartilage by these cytokines, could provide a mechanism for the chronic nature of rheumatoid disease.