Baker D G, Krakauer K A, Tate G, Laposata M, Zurier R B
Department of Medicine (Rheumatology Section), University of Pennsylvania, Philadelphia.
Arthritis Rheum. 1989 Oct;32(10):1273-81. doi: 10.1002/anr.1780321013.
Prostaglandin E1 (PGE1) and oils enriched in its precursor fatty acids suppress inflammation and joint tissue injury in several animal models. Since synovial cell proliferation is a hallmark of rheumatoid arthritis, we studied the effect of dihomo-gamma-linolenic acid (DGLA), an immediate precursor of PGE1, on the growth of human adherent synovial cells (ASC) in tissue culture. When stimulated by appropriate concentrations of recombinant interleukin-1 beta (rIL-1 beta), ASC proliferate and produce PGE. DGLA-enriched medium suppressed both baseline and rIL-1 beta-stimulated ASC growth fivefold, compared with medium supplemented with arachidonic acid. Indomethacin reduced the effect of the DGLA. Synovial cells incorporated the DGLA, and rIL-1 beta-stimulated cells that were incubated with DGLA exhibited a 14-fold increase in PGE1 (to 25.2 +/- 6.0 ng/ml, mean +/- SD) and a 70% decrease in PGE2 (to 25.2 +/- 4.2 ng/ml) compared with cells in control medium. At equivalent concentrations (5 x 10(-7) M), PGE1 increased the level of cellular cAMP to a greater extent than did PGE2 (16.8 +/- 2.0 pmoles versus 4.3 +/- 1.9 pmoles, mean +/- SEM). Exogenous PGE1 was also a more effective inhibitor of cell growth. Similarly, cAMP concentrations in cells exposed to DGLA for 6 hours were greater than concentrations in arachidonic acid-enriched cultures (17.8 +/- 3.3 pmoles versus 2.1 +/- 2.0 pmoles). These observations suggest that DGLA can restrain ASC growth, an effect which may be due to its capacity to increase PGE1 production and subsequent cellular cAMP concentration.
前列腺素E1（PGE1）及其前体脂肪酸含量丰富的油类可在多种动物模型中抑制炎症和关节组织损伤。由于滑膜细胞增殖是类风湿性关节炎的一个标志，我们研究了PGE1的直接前体二高-γ-亚麻酸（DGLA）对组织培养中人类贴壁滑膜细胞（ASC）生长的影响。当受到适当浓度的重组白细胞介素-1β（rIL-1β）刺激时，ASC会增殖并产生PGE。与添加花生四烯酸的培养基相比，富含DGLA的培养基可将基线和rIL-1β刺激的ASC生长抑制五倍。吲哚美辛降低了DGLA的作用。滑膜细胞摄取了DGLA，与对照培养基中的细胞相比，用DGLA孵育的rIL-1β刺激细胞的PGE1增加了14倍（至25.2±6.0 ng/ml，平均值±标准差），PGE2减少了70%（至25.2±4.2 ng/ml）。在等效浓度（5×10⁻⁷ M）下，PGE1比PGE2更能提高细胞内cAMP水平（16.8±2.0皮摩尔对4.3±1.9皮摩尔，平均值±标准误）。外源性PGE1也是更有效的细胞生长抑制剂。同样，暴露于DGLA 6小时的细胞中的cAMP浓度高于富含花生四烯酸的培养物中的浓度（17.8±3.3皮摩尔对2.1±2.0皮摩尔）。这些观察结果表明，DGLA可以抑制ASC生长，这种作用可能归因于其增加PGE1产生及随后细胞内cAMP浓度的能力。
