Candela M, Barker S C, Ballou L R
Department of Medicine, University of Tennessee, Memphis 38163.
Mol Cell Biochem. 1993 Mar 10;120(1):43-50. doi: 10.1007/BF00925983.
To examine the possible role of basic fibroblast growth factor (FGF) in regulating the effects of TNF alpha, we tested the effect of FGF on TNF alpha-mediated PGE2 production and TNF alpha receptor expression in human fibroblasts. We found that, while FGF alone had no effect on PGE2 production, it enhanced the amount of PGE2 produced in response to TNF alpha between 3 and 11-fold. FGF stimulated TNF alpha-induced PGE2 production independent of potential TNF alpha-mediated IL-1 production, as neither anti-IL-1 mAbs nor IL-1 receptor antagonist protein (IRAP) inhibited TNF alpha induced-PGE2 production or the stimulatory effect of FGF. A one minute exposure of cells to FGF prior to removal was sufficient to significantly enhance TNF alpha-induced PGE2 production; the maximal FGF effect was reached after a 6 h preincubation. We also found that FGF significantly enhanced TNF alpha receptor expression. Untreated fibroblasts expressed approximately 3,900 receptors/cell, while cells treated with FGF for 6 h expressed approximately 9,500 receptors/cell, a 2.4-fold increase in receptor number; there was no apparent change in affinity for TNF alpha (Kd 3.8 x 10(-11) M). The FGF-mediated increase in TNF alpha receptor expression and TNF alpha-mediated PGE2 production could be abolished by FGF mAbs, indicating a specific FGF effect. These results show that FGF increases TNF alpha receptor expression and suggest that this may account, at least in part, for the ability of FGF to enhance TNF alpha-mediated PGE2 production in human fibroblasts.
为了研究碱性成纤维细胞生长因子（FGF）在调节肿瘤坏死因子α（TNFα）作用中的潜在作用，我们检测了FGF对人成纤维细胞中TNFα介导的前列腺素E2（PGE2）产生及TNFα受体表达的影响。我们发现，虽然单独的FGF对PGE2产生没有影响，但它能将TNFα刺激产生的PGE2量提高3至11倍。FGF刺激TNFα诱导的PGE2产生，且不依赖于潜在的TNFα介导的白细胞介素-1（IL-1）产生，因为抗IL-1单克隆抗体和IL-1受体拮抗剂蛋白（IRAP）均不能抑制TNFα诱导的PGE2产生或FGF的刺激作用。在去除FGF之前让细胞暴露1分钟就足以显著增强TNFα诱导的PGE2产生；预孵育6小时后达到FGF的最大效应。我们还发现FGF能显著增强TNFα受体的表达。未处理的成纤维细胞每个细胞表达约3900个受体，而用FGF处理6小时的细胞每个细胞表达约9500个受体，受体数量增加了2.4倍；对TNFα的亲和力（解离常数Kd为3.8×10⁻¹¹M）没有明显变化。FGF单克隆抗体可消除FGF介导的TNFα受体表达增加及TNFα介导的PGE2产生，表明这是FGF的特异性作用。这些结果表明FGF增加了TNFα受体的表达，并提示这可能至少部分解释了FGF增强人成纤维细胞中TNFα介导的PGE2产生的能力。
