Wallington L A, Durham J, Bunce C M, Drayson M T, Brown G
Department of Immunology, The Medical School, University of Birmingham, Edgbaston, U.K.
Leuk Res. 1997 Jul;21(7):623-34. doi: 10.1016/s0145-2126(97)00021-0.
Sensitivity of the human promyeloid cell line HL60 to physiological differentiating agents [e.g. all-trans retinoic acid (all-trans RA) and 1 alpha, 25-dihydroxyvitamin (D3)] is increased by exposure of cells to "anti-inflammatory agents" (e.g. indomethacin) and to steroids [e.g. medroxyprogesterone acetate (MPA)] and post "priming" with a low dose (10(-8) M) of all-trans RA. Co-treatment of serum free-grown HL60 cells (HL60-ITS) with indomethacin and D3 reduces the dose of D3 required for monocyte differentiation from 10(-7) to 6.25 x 10(-9) M. This potentiating effect was observed to be almost absent when experiments where undertaken using serum-grown HL60 cells (HL60-FCS). The agent present in serum that interferes with indomethacin- and MPA-potentiation of the sensitivity of HL60 cells to D3 has been identified as the thyroid hormone 3,5,3'-L-triiodothyronine (T3). "Priming" of HL60-ITS cells with a low dose of all-trans RA reduces the amount of D3 required for the induction of monocyte differentiation to the same degree as co-treatment with either indomethacin or MPA (to 5 x 10(-9) M). However, the combined effect of all-trans RA "priming" and T3 treatment of HL60-ITS cells was induction of apoptosis. Treatment with either agent alone did not result in increased levels of apoptotic cells. These data reveal that T3 has an important influence on the capacity of HL60 cells to undergo differentiation and can promote apoptosis of these cells. Drug combinations, such as a differentiation potentiating agent, for example, indomethacin or MPA, and a differentiation inducer, for example, all-trans RA or D3, may have important therapeutic significance. Serum levels of T3 would be anticipated to influence the outcome.
人早幼粒细胞系HL60对生理分化剂[如全反式维甲酸（全反式RA）和1α，25-二羟基维生素D3]的敏感性，可通过将细胞暴露于“抗炎剂”（如吲哚美辛）、类固醇[如醋酸甲羟孕酮（MPA）]以及用低剂量（10^(-8)M）的全反式RA进行“预刺激”而增加。用吲哚美辛和D3共同处理无血清培养的HL60细胞（HL60-ITS），可将单核细胞分化所需的D3剂量从10^(-7)M降至6.25×10^(-9)M。当使用含血清培养的HL60细胞（HL60-FCS）进行实验时，几乎未观察到这种增强作用。已确定血清中干扰吲哚美辛和MPA增强HL60细胞对D3敏感性的物质是甲状腺激素3,5,3'-L-三碘甲状腺原氨酸（T3）。用低剂量的全反式RA对HL60-ITS细胞进行“预刺激”，与用吲哚美辛或MPA共同处理一样，可将诱导单核细胞分化所需的D3量降至相同程度（至5×10^(-9)M）。然而，全反式RA“预刺激”和T3处理HL60-ITS细胞的联合作用是诱导细胞凋亡。单独使用任何一种试剂处理都不会导致凋亡细胞水平增加。这些数据表明，T3对HL60细胞的分化能力有重要影响，并可促进这些细胞的凋亡。药物组合，如分化增强剂（如吲哚美辛或MPA）和分化诱导剂（如全反式RA或D3），可能具有重要的治疗意义。预计血清T3水平会影响治疗结果。
