Saitoh O, Matsuse R, Sugi K, Nakagawa K, Uchida K, Maemura K, Kojima K, Hirata I, Katsu K
Second Department of Internal Medicine, Osaka Medical College, Japan.
J Gastroenterol. 1997 Oct;32(5):605-10. doi: 10.1007/BF02934109.
Intestinal epithelial cells produce various inflammatory mediators. However, the way in which immunosuppressive agents influence the production of these mediators by intestinal epithelial cells is not understood. The effects of cyclosporine A (CsA), tacrolimus (FK506), and dexamethasone (DEX) on cytokine-induced production of interleukin (IL)-8 in a human colonic cancer cell line (HT-29) were examined. HT-29 cells were stimulated with either IL-1 beta or tumor necrosis factor alpha (TNF alpha) together with CsA, FK506, or DEX. The presence of IL-8 protein was detected by enzyme-linked immunosorbent assay, and the expression of IL-8 messenger RNA (mRNA) by reversetranscription polymerase chain reaction. CsA (1, 5, and 10ng/ml) significantly reduced IL-1 beta-induced IL-8 production (by 32%, 41%, and 48%, respectively), and reduced TNF alpha-induced IL-8 production (by 21%, 42%, and 50%, respectively). FK506 or DEX had no effect on IL-1 beta- or TNF alpha-induced IL-8 production. The expression of IL-8 mRNA was also inhibited by CsA. These findings suggest that CsA may influence the production of inflammatory mediators in colonic cells in a different manner from FK506 and DEX.
肠道上皮细胞会产生多种炎症介质。然而，免疫抑制剂影响肠道上皮细胞产生这些介质的方式尚不清楚。研究了环孢素A（CsA）、他克莫司（FK506）和地塞米松（DEX）对人结肠癌细胞系（HT - 29）中细胞因子诱导的白细胞介素（IL）- 8产生的影响。用IL - 1β或肿瘤坏死因子α（TNFα）联合CsA、FK506或DEX刺激HT - 29细胞。通过酶联免疫吸附测定法检测IL - 8蛋白的存在，并通过逆转录聚合酶链反应检测IL - 8信使核糖核酸（mRNA）的表达。CsA（1、5和10 ng/ml）显著降低IL - 1β诱导的IL - 8产生（分别降低32%、41%和48%），并降低TNFα诱导的IL - 8产生（分别降低21%、42%和50%）。FK506或DEX对IL - 1β或TNFα诱导的IL - 8产生没有影响。CsA也抑制IL - 8 mRNA的表达。这些发现表明，CsA可能以与FK506和DEX不同的方式影响结肠细胞中炎症介质的产生。
