Diaz A, Chepenik K P, Korn J H, Reginato A M, Jimenez S A
Department of Medicine, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
Exp Cell Res. 1998 May 25;241(1):222-9. doi: 10.1006/excr.1998.4050.
In the present studies we found that incubation of human lung fibroblasts with transforming growth factor-beta 1 (TGF-beta 1) potentiated the interleukin-1 beta (IL-1 beta) and/or tumor necrosis factor-alpha (TNF-alpha)-stimulated production of prostaglandin E2 (PGE2). Analysis of fibroblast proteins showed the induction of cyclooxygenase-1 (Cox-1) by TGF-beta 1 and the induction of Cox-2 by IL-1 beta and TNF-alpha. The levels of transcripts for Cox-1 were minimally modified by IL-1 beta or TNF-alpha, however, they were increased by 12-fold by TGF-beta 1. Transcripts for Cox-2 were induced by IL-1 beta or TNF-alpha and their induction was potentiated by TGF-beta 1. TGF-beta 1 alone did not induce Cox-2 transcripts. In vitro transcription assays showed that IL-1 beta and TNF-alpha increased the transcription of the Cox-2 gene, whereas TGF-beta 1 had no effect. Addition of TGF-beta did not increase further the transcription of Cox-2 in IL-1 beta-treated cells, but increased the stability of the corresponding transcripts. The transcription rate of the Cox-1 gene was not increased by any of the cytokines studied. In summary, we demonstrate that the potentiation of PGE2 production by TGF-beta 1 in IL-1 beta and TNF-alpha-treated fibroblasts is the result of transcriptional stimulation of the Cox-2 gene by IL-1 beta and TNF-alpha and the stabilization of the resulting transcripts by TGF-beta 1.
在本研究中，我们发现用转化生长因子-β1（TGF-β1）孵育人肺成纤维细胞可增强白细胞介素-1β（IL-1β）和/或肿瘤坏死因子-α（TNF-α）刺激的前列腺素E2（PGE2）的产生。对成纤维细胞蛋白的分析显示，TGF-β1可诱导环氧合酶-1（Cox-1），IL-1β和TNF-α可诱导Cox-2。IL-1β或TNF-α对Cox-1转录本水平的影响极小，然而，TGF-β1可使其增加12倍。Cox-2转录本由IL-1β或TNF-α诱导，且TGF-β1可增强其诱导作用。单独的TGF-β1不诱导Cox-2转录本。体外转录分析显示，IL-1β和TNF-α可增加Cox-2基因的转录，而TGF-β1无此作用。添加TGF-β不会进一步增加IL-1β处理细胞中Cox-2的转录，但会增加相应转录本的稳定性。所研究的任何细胞因子均未增加Cox-1基因的转录速率。总之，我们证明在IL-1β和TNF-α处理的成纤维细胞中，TGF-β1对PGE2产生的增强作用是IL-1β和TNF-α对Cox-2基因转录刺激以及TGF-β1对所得转录本稳定作用的结果。
