Kumkumian G K, Lafyatis R, Remmers E F, Case J P, Kim S J, Wilder R L
Arthritis and Rheumatism Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, MD 20892.
J Immunol. 1989 Aug 1;143(3):833-7.
We show that platelet-derived growth factor (PDGF) and IL-1 interact in both a synergistic and antagonistic manner to regulate synovial fibroblast-like cells (synoviocytes) derived from patients with rheumatoid arthritis. PDGF and IL-1 operated synergistically in vitro to stimulate synoviocyte proliferation in the presence of indomethacin. However, when these same cells were treated with PDGF and IL-1 in the absence of indomethacin, IL-1 inhibited PDGF-stimulated synoviocyte proliferation. Moreover, exogenous PGE2, a PG known to be produced in response to IL-1, dramatically inhibited synoviocyte proliferation induced by PDGF. PDGF also acted synergistically to markedly increase production of PGE2 stimulated by IL-1. This is in contrast to the antagonistic effect PDGF had on IL-1-stimulated collagenase transcription. IL-1 stimulated collagenase transcription, but PDGF did not. It in fact inhibited IL-1 stimulation of collagenase gene expression. These data differ somewhat from those reported for dermal fibroblasts. Our data further indicate that the effects of cytokines vary from one cell type to another, even amongst "fibroblasts," and illustrate the complexity of cytokine regulation of rheumatoid synoviocyte function.
我们发现，血小板衍生生长因子（PDGF）和白细胞介素-1（IL-1）以协同和拮抗的方式相互作用，以调节类风湿性关节炎患者来源的滑膜成纤维样细胞（滑膜细胞）。在吲哚美辛存在的情况下，PDGF和IL-1在体外协同作用以刺激滑膜细胞增殖。然而，当在没有吲哚美辛的情况下用PDGF和IL-1处理这些相同的细胞时，IL-1抑制PDGF刺激的滑膜细胞增殖。此外，外源性前列腺素E2（PGE2）是一种已知因IL-1而产生的前列腺素，它显著抑制PDGF诱导的滑膜细胞增殖。PDGF还协同作用，显著增加IL-1刺激的PGE2的产生。这与PDGF对IL-1刺激的胶原酶转录的拮抗作用形成对比。IL-1刺激胶原酶转录，但PDGF不刺激。事实上，它抑制IL-1对胶原酶基因表达的刺激。这些数据与报道的真皮成纤维细胞的数据有些不同。我们的数据进一步表明，细胞因子的作用因细胞类型而异，即使在“成纤维细胞”中也是如此，并说明了细胞因子对类风湿性滑膜细胞功能调节的复杂性。
