Sacco O, Romberger D, Rizzino A, Beckmann J D, Rennard S I, Spurzem J R
Research Service Department of Veteran Affairs Medical Center, Omaha, Nebraska 68105.
J Clin Invest. 1992 Oct;90(4):1379-85. doi: 10.1172/JCI116004.
The ability of airway epithelial cells to produce transforming growth factor-beta (TGF-beta) may be an important mechanism for the control of growth, differentiation, and repair of the airway epithelium. To determine whether airway epithelial cells are capable of producing TGF-beta, we examined primary cultures of bovine bronchial epithelial cells. Using a bioassay, TGF-beta activity was detected readily in media conditioned by bovine bronchial epithelial cells. Neutralizing antisera to TGF-beta 1 and TGF-beta 2 were used to demonstrate that the majority of the activity was of the TGF-beta 2 isoform. Interestingly, some of the TGF-beta activity was present in the conditioned media as "active" TGF-beta, not requiring acid activation. The production of TGF-beta was variable, depending on cell density and the presence of retinoic acid. The presence of endogenously produced active TGF-beta in the culture media was shown to modulate the behavior of the cell cultures as evidenced by the effects of TGF-beta-neutralizing antisera on cell size and fibronectin production. Our results suggest that active TGF-beta produced by airway epithelial cells may function in an autocrine or paracrine manner to modulate epithelial cell behavior.
气道上皮细胞产生转化生长因子-β(TGF-β)的能力可能是控制气道上皮生长、分化和修复的重要机制。为了确定气道上皮细胞是否能够产生TGF-β,我们检测了牛支气管上皮细胞的原代培养物。通过生物测定法,在牛支气管上皮细胞条件培养基中很容易检测到TGF-β活性。使用针对TGF-β1和TGF-β2的中和抗血清来证明大部分活性是TGF-β2亚型。有趣的是,一些TGF-β活性以“活性”TGF-β的形式存在于条件培养基中,不需要酸激活。TGF-β的产生是可变的,取决于细胞密度和视黄酸的存在。培养基中内源性产生的活性TGF-β的存在被证明可调节细胞培养物的行为,TGF-β中和抗血清对细胞大小和纤连蛋白产生的影响证明了这一点。我们的结果表明,气道上皮细胞产生的活性TGF-β可能以自分泌或旁分泌方式发挥作用,调节上皮细胞行为。