Expression of Interleukin-6 and Its Effects on Growth of HP75 Human Pituitary Tumor Cells

• Published in: The journal of clinical endocrinology and metabolism 2003-10, Vol.88 (10), p.4938-4944
• Main Authors: Borg, S. A., Kerry, K. E., Baxter, L., Royds, J. A., Jones, T. H.
• Format: Article
• Language: English
• Subjects: Adenoma; Biological and medical sciences; Cell Division - drug effects; Cell Division - physiology; Endocrinopathies; Gene Expression; Humans; Hypothalamus. Hypophysis. Epiphysis (diseases); Immunohistochemistry; Interleukin-6 - genetics; Interleukin-6 - pharmacology; Interleukin-6 - secretion; Medical sciences; Non tumoral diseases. Target tissue resistance. Benign neoplasms; Pituitary Neoplasms; Receptors, Interleukin-6 - genetics; RNA, Messenger - analysis; Tropical medicine; Tumor Cells, Cultured - cytology; Tumor Cells, Cultured - physiology; Tumor Cells, Cultured - secretion
• ISSN: 0021-972X; 1945-7197
• 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-1α 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.