Melanoma growth-stimulatory activity/GRO decreases collagen expression by human fibroblasts. Regulation by C-X-C but not C-C cytokines.
Melanoma growth-stimulatory activity/GRO decreases collagen expression by human fibroblasts. Regulation by C-X-C but not C-C cytokines.
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DOI：
10.1016/s0021-9258(18)54080-1
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发表时间：
1993-01
期刊：
影响因子：
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通讯作者：
E. Unemori;E. Amento;E. Bauer;R. Horuk
中科院分区：
文献类型：
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作者：
E. Unemori;E. Amento;E. Bauer;R. Horuk
黑色素瘤生长刺激活性（MGSA）/GRO被充分表征为有效的中性粒细胞化学引诱物。在本研究中，我们已经证明，MGSA诱导类风湿性滑膜成纤维细胞间质胶原表达的剂量依赖性降低。在0.6-6.0 nM MGSA的剂量范围内观察到降低。这种作用是特异性的，因为MGSA对胶原降解金属蛋白酶的表达没有明显的作用，也不影响胶原酶抑制剂、金属蛋白酶的组织抑制剂。它对这些成纤维细胞的增殖率也没有影响，不像它对黑色素瘤细胞的促有丝分裂作用。血小板因子4超家族C-X-C分支的另一个成员白细胞介素-8（IL-8）也证明了抑制胶原蛋白表达的能力，但属于C-C分支的RANTES、MIP-1 α或MIP-1 β则没有。正常成人组织中MGSA和IL-8转录物的稳态表达水平是不同的，这表明表达可能是这些细胞因子的活性受到调节的重要水平。用125 I-MGSA对滑膜成纤维细胞进行的直接结合实验使我们能够鉴定出具有10.1 nM KD和约75，000个结合位点/成纤维细胞的MGSA受体。125 I-MGSA结合是特异性的，不能被未标记的IL-8取代。这些结果表明，MGSA，以及IL-8，可能发挥的作用以外的中性粒细胞的化学引诱剂，更具体地说，可能是重要的胶原蛋白周转的调节。
Melanoma growth-stimulatory activity (MGSA)/GRO is well characterized as a potent neutrophil chemoattractant. In the present study, we have demonstrated that MGSA induced a dose-dependent decrease in the expression of interstitial collagens by rheumatoid synovial fibroblasts. The decrease was observed over a dose range of 0.6-6.0 nM MGSA. This effect was specific, as MGSA had no demonstrable effect on the expression of collagen-degrading metalloproteinases, nor did it affect the collagenase inhibitor, tissue inhibitor of metalloproteinases. It also had no effect on the proliferation rate of these fibroblasts, unlike its mitogenic effect on melanoma cells. The ability to inhibit collagen expression was also demonstrated by another member of the C-X-C branch of the platelet factor 4 superfamily, interleukin-8 (IL-8), but not by RANTES, MIP-1 alpha, or MIP-1 beta, which belong to the C-C branch. Steady-state levels of expression of MGSA and IL-8 transcripts in normal adult tissues were dissimilar, suggesting that expression may be an important level at which the activity of these cytokines is regulated. Direct binding experiments with 125I-MGSA on synovial fibroblasts have allowed us to identify an MGSA receptor with a KD of 10.1 nM and approximately 75,000 binding sites/fibroblast. 125I-MGSA binding was specific and could not be displaced by unlabeled IL-8. These results suggest that MGSA, as well as IL-8, may play a role other than that of neutrophil chemo-attractant and more specifically, may be important in the regulation of collagen turnover.