Effect of interleukin-1 beta on aromatase activity and cell proliferation in human osteoblast-like cells (HOS)

Osteoblast cells have a capacity to produce estrogen from androgen. Pt is k nown that inflammatory cytokines in bone increase during estrogen deficienc y. In the present study, the effect of interleukin-1 beta (IL-1 beta) on ar omatase (Arom) activity in human osteoblast-like cells (HOS) was investigat ed. We also investigated the effect of IL-1 beta and estradiol (E2) on cell proliferation in NOS. [H-3] water method was employed to measure Arom acti vity. Expression of Arom mRNA was determined by the reverse-transcription p olymerase chain reaction (RT-PCR) method. The PCR products were confirmed b y Southern blot analysis. Cell proliferation was measured by an ELISA-bromo deoxyuridine (BrdU) kit. Addition of IL-1 beta increased Arom activity in a dose-dependent manner and addition of IL-1 beta (10 ng/ml) resulted in 40 % greater activity than control. Addition of 500 ng/ml of human recombinant IL-1 receptor antagonist neutralized the increased Arom activity to contro l level. Stimulation of Arom mRNA expression by IL-1 beta was also found. I L-1 beta and E2 stimulate osteoblastic cell proliferation significantly. Th ese findings suggest for the first time that IL-1 beta stimulates Arom acti vity through the IL-1 receptor and also cell proliferation in osteoblast-li ke cells. It is also demonstrated that this stimulatory effect may be throu gh the IL-1 receptor. Cell proliferation stimulated by IL-1 beta was reduce d by the addition of the Arom inhibitor fadrozole-HCL (CGS-16949A). These r esults imply that IL-1 beta has a stimulatory effect on estrogen formation and sequentially cell proliferation in bone, and this mechanism may play an important role in osteoblastic function especially in postmenopausal women . (C) 2000 Academic Press.