Biochemical and Biophysical Research Communications, Vol.268, No.1, 60-64, 2000
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 known that inflammatory cytokines in bone increase during estrogen deficiency. In the present study, the effect of interleukin-1 beta (IL-1 beta) on aromatase (Arom) activity in human osteoblast-like cells (HOS) was investigated. 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 activity. Expression of Arom mRNA was determined by the reverse-transcription polymerase chain reaction (RT-PCR) method. The PCR products were confirmed by 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 control level. Stimulation of Arom mRNA expression by IL-1 beta was also found. IL-1 beta and E2 stimulate osteoblastic cell proliferation significantly. These findings suggest for the first time that IL-1 beta stimulates Arom activity through the IL-1 receptor and also cell proliferation in osteoblast-like cells. It is also demonstrated that this stimulatory effect may be through the IL-1 receptor. Cell proliferation stimulated by IL-1 beta was reduced by the addition of the Arom inhibitor fadrozole-HCL (CGS-16949A). These results 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.