Expression of interleukin-6 and its effects on growth of HP75 human pituitary tumor cells.
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.
Borg
S A
SA
Endocrine Heart and Pituitary Group, Academic Unit of Endocrinology, Division of Genomic Medicine, University of Sheffield Medical School, Sheffield, United Kingdom S10 2RX.
Kerry
K E
KE
Baxter
L
L
Royds
J A
JA
Jones
T H
TH
D000236:Adenoma; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D015850:Interleukin-6 / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology; D010911:Pituitary Neoplasms; D012333:RNA, Messenger / Q000032:analysis; D019947:Receptors, Interleukin-6 / Q000235:genetics; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000378:metabolism / Q000502:physiology
D015850:Interleukin-6; D012333:RNA, Messenger; D019947:Receptors, Interleukin-6