Nb2淋巴瘤细胞中糖皮质激素与催乳素的相互作用：抗增殖与抗细胞溶解作用

Glucocorticoid-prolactin interactions in Nb2 lymphoma cells: antiproliferative versus anticytolytic effects.

作者信息

Fletcher-Chiappini S E, Compton M M, LaVoie H A, Day E B, Witorsch R J

机构信息

Department of Physiology, School of Basic Health Sciences, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298.

出版信息

Proc Soc Exp Biol Med. 1993 Mar;202(3):345-52. doi: 10.3181/00379727-202-43545.

DOI:10.3181/00379727-202-43545

PMID:8437991

Abstract

The interaction between the immunosuppressive effects of glucocorticoids and the mitogenic effects of prolactin (PRL) were examined in Nb2 lymphoma cells, a pre-T cell line. The synthetic glucocorticoid, dexamethasone (Dex), caused a concentration-dependent (6.25-200 nM) inhibition of basal and ovine PRL (oPRL)-stimulated Nb2 cell proliferation. Although Dex was antiproliferative, the steroid had no effect on cell viability in the presence of PRL. However, when PRL was omitted from the medium, Dex increased the proportion of dead Nb2 cells by 24 hr in a concentration (25-200 nM)-dependent fashion without affecting total cell number. The antiproliferative and cytolytic effects of Dex were mimicked by other corticosteroids (cortisol, corticosterone, aldosterone, and deoxycorticosterone) in the expected order of glucocorticoid potency, but not by other steroids (17-beta-estradiol, progesterone, testosterone, 5-alpha-dihydrotestosterone, and dehydroepiandrosterone) or triiodothyronine. In addition, the antiproliferative and cytolytic effects of glucocorticoids were antagonized by the glucocorticoid receptor antagonist RU 486. Since corticosteroid-induced cytolysis was apparent only in the absence of mitogen, the anticytolytic effects of oPRL were tested. In the presence of Dex (100 nM), oPRL (25-1600 pg/ml) caused a concentration-dependent inhibition of cytolysis without changing cell number. Other lactogenic hormones (human growth hormone, human placental lactogen, rat PRL), but not trophic nonlactogenic hormones (rat growth hormone, human chorionic gonadotropin, ACTH), also inhibited Dex (100 nM)-induced cytolysis. Agarose gel electrophoresis of DNA extracted from Nb2 cells revealed that within 12 hr, 100 nM Dex induced DNA fragmentation, indicative of programmed cell death or apoptosis. Coincubation of cells with Dex and oPRL (1 ng/ml) inhibited Dex-induced fragmentation of Nb2 cell genomic DNA. These studies reveal a complex interaction between glucocorticoids and PRL in Nb2 cells. Although a glucocorticoid receptor-mediated antiproliferative effect is evident, PRL (at concentrations that usually stimulate cell proliferation) has the capacity to protect the cell against glucocorticoid-receptor-mediated induction of apoptosis.

摘要

在Nb2淋巴瘤细胞（一种前T细胞系）中研究了糖皮质激素的免疫抑制作用与催乳素（PRL）的促有丝分裂作用之间的相互作用。合成糖皮质激素地塞米松（Dex）对基础状态及绵羊PRL（oPRL）刺激的Nb2细胞增殖产生浓度依赖性（6.25 - 200 nM）抑制。尽管Dex具有抗增殖作用，但在有PRL存在时该类固醇对细胞活力无影响。然而，当培养基中省略PRL时，Dex以浓度（25 - 200 nM）依赖性方式在24小时内增加了死亡Nb2细胞的比例，而不影响细胞总数。Dex的抗增殖和细胞溶解作用可被其他皮质类固醇（皮质醇、皮质酮、醛固酮和脱氧皮质酮）以预期的糖皮质激素效力顺序模拟，但不能被其他类固醇（17-β-雌二醇、孕酮、睾酮、5-α-二氢睾酮和脱氢表雄酮）或三碘甲状腺原氨酸模拟。此外糖皮质激素受体拮抗剂RU 486可拮抗糖皮质激素的抗增殖和细胞溶解作用。由于皮质类固醇诱导的细胞溶解仅在无促有丝分裂原时明显，因此测试了oPRL的抗细胞溶解作用。在存在Dex（100 nM）的情况下，oPRL（25 - 1600 pg/ml）产生浓度依赖性的细胞溶解抑制作用，而不改变细胞数量。其他催乳激素（人生长激素、人胎盘催乳素、大鼠PRL），但不是营养性非催乳激素（大鼠生长激素、人绒毛膜促性腺激素、促肾上腺皮质激素），也抑制Dex（1 nM）诱导的细胞溶解。从Nb2细胞提取的DNA的琼脂糖凝胶电泳显示，在12小时内，100 nM Dex诱导DNA片段化，表明程序性细胞死亡或凋亡。细胞与Dex和oPRL（1 ng/ml）共同孵育可抑制Dex诱导的Nb2细胞基因组DNA片段化。这些研究揭示了Nb2细胞中糖皮质激素与PRL之间复杂的相互作用。尽管糖皮质激素受体介导的抗增殖作用明显，但PRL（在通常刺激细胞增殖的浓度下）有能力保护细胞免受糖皮质激素受体介导的凋亡诱导。