Borg S A, Kerry K E, Baxter L, Royds J A, Jones T H
Endocrine Heart and Pituitary Group, Academic Unit of Endocrinology, Division of Genomic Medicine, University of Sheffield Medical School, Sheffield, United Kingdom S10 2RX.
J Clin Endocrinol Metab. 2003 Oct;88(10):4938-44. doi: 10.1210/jc.2002-022044.
The role of IL-6 in the pathogenesis of pituitary adenomas is unclear, as tumor biology is difficult to study in primary culture. We have shown here that the human pituitary cell line HP75 synthesizes IL-6 mRNA and expresses and secretes IL-6 (6167 +/- 56 pg/ml/72 h for 30,000 cells). IL-6 receptor (IL-6R) mRNA was identified by in situ hybridization and RT-PCR. Exogenous IL-6 in low dose (1 ng/ml) stimulated, whereas higher doses (100 ng/ml) inhibited, growth. This diverse effect occurs in other cell types as a result of receptor down-regulation. Cell growth was inhibited by IL-6-blocking antibody (76 +/- 6.5% inhibition; P < 0.0001). This demonstrates that IL-6 is an important growth regulator in HP75 cells, having an autocrine growth stimulatory effect under basal conditions. IL-1alpha and dibutyryl cAMP stimulated and dexamethasone inhibited IL-6 secretion; however, bacterial lipopolysaccharide, forskolin, and cholera toxin had no effect. This implies that there is a defect in the control of IL-6 secretion. Soluble IL-6R was not detected, but soluble gp130 receptor was present in the conditioned medium. Stimulation of cleavage of soluble IL-6R from the membrane-bound IL-6R could not be induced by phorbol ester or dexamethasone. Whether IL-6 has a similar effect in human pituitary adenomas requires further investigation.
白细胞介素-6（IL-6）在垂体腺瘤发病机制中的作用尚不清楚，因为肿瘤生物学在原代培养中很难研究。我们在此表明，人垂体细胞系HP75能合成IL-6 mRNA，并表达和分泌IL-6（30000个细胞在72小时内分泌6167±56 pg/ml）。通过原位杂交和逆转录聚合酶链反应（RT-PCR）鉴定出IL-6受体（IL-6R）mRNA。低剂量（1 ng/ml）的外源性IL-6刺激生长，而高剂量（100 ng/ml）则抑制生长。由于受体下调，这种不同的效应在其他细胞类型中也会出现。IL-6阻断抗体抑制细胞生长（抑制率为76±6.5%；P<0.0001）。这表明IL-6是HP75细胞中一种重要的生长调节因子，在基础条件下具有自分泌生长刺激作用。白细胞介素-1α（IL-1α）和二丁酰环磷腺苷（dibutyryl cAMP）刺激IL-6分泌，地塞米松抑制IL-6分泌；然而，细菌脂多糖、福斯可林和霍乱毒素则无此作用。这意味着在IL-6分泌的控制方面存在缺陷。未检测到可溶性IL-6R，但条件培养基中存在可溶性gp130受体。佛波酯或地塞米松不能诱导从膜结合IL-6R上裂解出可溶性IL-6R。IL-6在人垂体腺瘤中是否有类似作用需要进一步研究。
