Effect of interleukin-1beta on aromatase activity and cell proliferation in human osteoblast-like cells (HOS).
Osteoblast cells have a capacity to produce estrogen from androgen. It is known that inflammatory cytokines in bone increase during estrogen deficiency. In the present study, the effect of interleukin-1beta (IL-1beta) on aromatase (Arom) activity in human osteoblast-like cells (HOS) was investigated. We also investigated the effect of IL-1beta and estradiol (E2) on cell proliferation in HOS. [(3)H] 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-1beta increased Arom activity in a dose-dependent manner and addition of IL-1beta (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-1beta was also found. IL-1beta and E2 stimulate osteoblastic cell proliferation significantly. These findings suggest for the first time that IL-1beta 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-1beta was reduced by the addition of the Arom inhibitor fadrozole-HCL (CGS-16949A). These results imply that IL-1beta 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.
Morioka
M
M
Department of Obstetrics and Gynecology, Showa University School of Medicine, 1-5-8, Hatanodai, Shinagawa-ku, Tokyo, 142-8666, Japan.
Shimodaira
K
K
Kuwano
Y
Y
Fujikawa
H
H
Saito
H
H
Yanaihara
T
T
D001141:Aromatase / Q000235:genetics / Q000378:metabolism*; D047072:Aromatase Inhibitors; D001483:Base Sequence; D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line; D017931:DNA Primers / Q000235:genetics; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology; D004967:Estrogens / Q000096:biosynthesis; D017316:Fadrozole / Q000494:pharmacology; D005260:Female; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000494:pharmacology*; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology*; D015663:Osteoporosis, Postmenopausal / Q000209:etiology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012795:Sialoglycoproteins / Q000494:pharmacology
D047072:Aromatase Inhibitors; D017931:DNA Primers; D004791:Enzyme Inhibitors; D004967:Estrogens; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D012333:RNA, Messenger; D012795:Sialoglycoproteins; D004958:Estradiol; D001141:Aromatase; D017316:Fadrozole