Warbrick E V, Thomas A L, Williams C M
Department of Pharmacology and Therapeutics, University of Liverpool, UK.
Toxicology. 1997 Jan 15;116(1-3):211-8. doi: 10.1016/s0300-483x(96)03519-6.
We examined by RT-PCR the effect of a number of immunomodulatory compounds on cytokine gene expression at the level of mRNA in the HMC-1 human leukemic mast cell line. Resting cells expressed relatively low constitutive levels of mRNA for the cytokine genes IL-3, IL-4 and IL-8, and mRNA levels for each of these cytokines were significantly enhanced after 4-h stimulation with the calcium ionophore ionomycin. Treatment of the cells with the immunosuppressant CsA at 10(-5) M produced a significant inhibition of ionomycin-induced expression of IL-3, IL-4 and IL-8 mRNA, and at 10(-6) M produced a significant inhibition of induced expression of IL-3 and IL-8 but not IL-4. At both concentrations of CsA, expression of IL-3 was inhibited to a greater extent than that of the other two cytokines. Treatment of the cells with the corticosteroid DEX at 10(-5) M but not 10(-6) M significantly reduced the ionomycin-induced expression of IL-3 but not IL-4 or IL-8 mRNA. Progesterone and methotrexate were both inactive in modulation of induced cytokine expression in this cell line. In conclusion, this study shows that cytokine expression, particularly of IL-3, is inhibited in a human mast cell line by CsA and DEX. These findings may be relevant to the anti-allergic action of these drugs.
我们通过逆转录聚合酶链反应（RT-PCR）检测了多种免疫调节化合物对人白血病肥大细胞系HMC-1中细胞因子基因在mRNA水平表达的影响。静息细胞中细胞因子基因白细胞介素-3（IL-3）、白细胞介素-4（IL-4）和白细胞介素-8（IL-8）的mRNA组成性表达水平相对较低，在用钙离子载体离子霉素刺激4小时后，这些细胞因子的mRNA水平均显著升高。用10⁻⁵ M的免疫抑制剂环孢素A（CsA）处理细胞，可显著抑制离子霉素诱导的IL-3、IL-4和IL-8 mRNA的表达；用10⁻⁶ M处理时，可显著抑制IL-3和IL-8的诱导表达，但对IL-4无影响。在这两种CsA浓度下，IL-3的表达受到的抑制程度均大于其他两种细胞因子。用10⁻⁵ M而非10⁻⁶ M的皮质类固醇地塞米松（DEX）处理细胞，可显著降低离子霉素诱导的IL-3 mRNA表达，但对IL-4或IL-8 mRNA无影响。孕酮和甲氨蝶呤在调节该细胞系中诱导的细胞因子表达方面均无活性。总之，本研究表明，CsA和DEX可抑制人肥大细胞系中的细胞因子表达，尤其是IL-3的表达。这些发现可能与这些药物的抗过敏作用有关。
