Elias J A, Lentz V, Cummings P J
Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06510.
J Immunol. 1991 May 15;146(10):3437-43.
We characterized the ability of transforming growth factor-beta 1 (TGF-beta 1) and transforming growth factor-beta 2 (TGF-beta 2) to regulate IL-6 production by unstimulated and rIL-1-stimulated lung fibroblasts. rTGF-beta 1-, purified TGF-beta 1-, and purified TGF-beta 2-stimulated fibroblasts produced IL-6 bioactivity as assessed with the B9 hybridoma proliferation assay. These TGF-beta moieties also bidirectionally regulated the IL-6 production of rIL-1-stimulated fibroblasts. The addition of TGF-beta to cultures in which fibroblasts were vigorously stimulated with rIL-1 resulted in an inhibition of fibroblast IL-6 production and mRNA accumulation. In contrast, the addition of TGF-beta to cultures in which fibroblasts were incubated with suboptimal concentrations of rIL-1 resulted in a synergistic increase in IL-6 production and mRNA accumulation [corrected]. Nuclear run-on analysis demonstrated that IL-6 gene [corrected] transcription was synergistically augmented when rTGF-beta 1 was combined with suboptimal concentrations of rIL-1. These studies demonstrate that TGF-beta stimulates fibroblast IL-6 production. They also show that TGF-beta can augment or inhibit the IL-6 production of IL-1-stimulated fibroblasts. Lastly, [corrected] they demonstrate that the stimulatory effects of TGF-beta are, at least partially, mediated by alterations in IL-6 gene transcription. TGF-beta may be an important regulator of IL-6 production. stimulated fibroblasts. Last, they demonstrate that the stimulatory effects of TGF-beta are, at least partially, mediated by alterations in IL-6 gene transcription. TGF-beta may be an important regulator of IL-6 production.
我们研究了转化生长因子-β1（TGF-β1）和转化生长因子-β2（TGF-β2）对未受刺激及经重组白细胞介素-1（rIL-1）刺激的肺成纤维细胞产生白细胞介素-6（IL-6）的调节能力。用B9杂交瘤增殖试验评估，重组TGF-β1、纯化的TGF-β1和纯化的TGF-β2刺激的成纤维细胞产生了IL-6生物活性。这些TGF-β部分还双向调节rIL-1刺激的成纤维细胞的IL-6产生。向用rIL-1强烈刺激成纤维细胞的培养物中添加TGF-β，导致成纤维细胞IL-6产生和mRNA积累受到抑制。相反，向用次优浓度rIL-1培养成纤维细胞的培养物中添加TGF-β，导致IL-6产生和mRNA积累协同增加[已修正]。核转录分析表明，当rTGF-β1与次优浓度的rIL-1联合使用时，IL-6基因[已修正]转录协同增强。这些研究表明TGF-β刺激成纤维细胞产生IL-6。它们还表明TGF-β可以增强或抑制IL-1刺激的成纤维细胞的IL-6产生。最后，[已修正]它们证明TGF-β的刺激作用至少部分由IL-6基因转录的改变介导。TGF-β可能是IL-6产生的重要调节因子。刺激的成纤维细胞。最后，它们证明TGF-β的刺激作用至少部分由IL-6基因转录的改变介导。TGF-β可能是IL-6产生的重要调节因子。
