Transforming growth factor-beta 1 is the predominant paracrine inhibitor of macrophage cytokine synthesis produced by glomerular mesangial cells .
Transforming growth factor-beta 1 is the predominant paracrine inhibitor of macrophage cytokine synthesis produced by glomerular mesangial cells .
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转化生长因子-β1 是肾小球系膜细胞产生的巨噬细胞细胞因子合成的主要旁分泌抑制剂。
作者：
M. Kitamura;T. Sütö;T. Yokoo;F. Shimizu;L. Fine
肾小球细胞与浸润性单核细胞之间的交叉通讯在肾小球疾病的发生或恢复中起重要作用。我们发现培养的系膜细胞分泌一种抑制活化巨噬细胞产生促炎细胞因子的因子。用来自大鼠系膜细胞的条件培养基处理J774.2巨噬细胞，可以减弱LPS对IL-1 β、IL-6和tnf - α的转录诱导。其他成纤维细胞、上皮细胞或内皮细胞系的培养基均未表现出抑制作用。正常大鼠肾小球调节的培养基含有类似的抑制活性，在系膜增生性肾小球肾炎急性模型中增强。为了确定所涉及的活性成分，我们检测了已知巨噬细胞失活剂IL-10、IL-13和tgf - β 1在系膜细胞中的表达。在基础培养条件下，观察到tgf - β 1 mRNA的强表达，而IL-10和IL-13均未表达。免疫印迹分析和特定的生物测定仅在系膜细胞条件培养基中检测到tgf - β 1的活性形式。热处理后抑制活性增强，与已知的tgf - β性质一致。一种特异性的抗tgf - β 1中和抗体消除了系膜细胞培养基的抑制作用，外源性添加tgf - β 1以剂量依赖性方式抑制巨噬细胞细胞因子的表达。这些发现表明系膜细胞和离体肾小球分泌一种抑制活化巨噬细胞细胞因子表达的因子，这种活性实体被确定为tgf - β 1。
Cross-communication between glomerular cells and infiltrating mononuclear cells plays an important role in the generation of or recovery from glomerular diseases. We found that cultured mesangial cells secrete a factor that inhibits production of proinflammatory cytokines by activated macrophages. Treatment of J774.2 macrophages with conditioned media from rat mesangial cells blunted the transcriptional induction of IL-1 beta, IL-6, and TNF-alpha by LPS. None of the media conditioned by other fibroblastic, epithelial, or endothelial cell lines exhibited the inhibitory effect. Media conditioned by normal rat glomeruli contained a similar inhibitory activity, which was enhanced in an acute model of mesangial proliferative glomerulonephritis. To identify the active component involved, we examined the expression of known macrophage deactivators IL-10, IL-13, and TGF-beta 1 in mesangial cells. Under the basal culture conditions, strong expression of TGF-beta 1 mRNA was observed, whereas expression of neither IL-10 nor IL-13 was detected. Immunoblot analysis and a specific bioassay detected the active form of TGF-beta 1 exclusively in the mesangial cell conditioned media. The inhibitory activity was enhanced by heat treatment, consistent with the known property of TGF-beta. A specific anti-TGF-beta 1 neutralizing Ab abolished the inhibitory effect exerted by the mesangial cell media, and exogenously added TGF-beta1 suppressed macrophage cytokine expression in a dose-dependent manner. These findings demonstrate that mesangial cells and isolated glomeruli secrete a factor which suppresses cytokine expression by activated macrophages, the active entity being identified as TGF-beta 1.