Korean J Bone Metab > Volume 14(2); 2007 > Article
Korean Journal of Bone Metabolism 2007;14(2):141-147.
Eosinophil Chemotactic Factor-L (ECF-L) Blocks The Suppressive Effects of IL-12 On Osteoclast Formation
파골세포에 IL-12의 작용을 억제함으로써 파골세포의 분화를 촉진하는 ECF-L의 효과
정호연
경희대학교 의과대학 내과학교실
Abstract
Objective
Osteoclast (OCL) formation and bone destruction is increased in inflammatory conditions such as rheumatoid arthritis (RA). This bone destruction occurs even though known inhibitors of OCL such as IL-12, IFN-γ and IL-4 are produced by activated T-cells in the affected joints. Recently, we identified ECF-L as a novel autocrine stimulator of OCL produced by monocytes/macrophages and OCL. It is our hypothesis that other factors produced in RA joints block the activity of these inhibitors of OCL formation. Therefore, we determined if ECF-L could block the inhibitory effect of IL-12 on OCL formation.
Methods
Purified ECF-L Fc fusion protein was added to murine bone marrow cultures in the presence or absence of IL-12. The effects of ECF-L on IL-12, and IL-12 receptor production and IL-12 receptor signaling were examined using PHA-stimulated non-adherent spleen cells as a source of lymphocytes. We determined if ECF-L increased cox-2 protein levels.
Results
ECF-L increased OCL-like cell formation in a dose-dependent manner in mouse marrow cultures compared to control cultures and blocked the inhibitory effects of IL-12 on OCL formation. ECF-L markedly decreased IL-12 R β1 mRNA expression by 80% and decreased IL-12 R β1 protein expression by 40% in PHA-activated spleen cells compared to control treatments. This decrease in IL-12 receptor expression resulted in a 70% decrease in IL-12-induced IFN-γ mRNA expression in spleen cells, as assessed by RT-PCR. Although STAT4 signaling was not decreased by simultaneous treatment of PHA activated spleen cell cultures with ECF-L and IL-12, STAT4 signaling was decreased by 30% when the cultures were pretreated with ECF-L for 24 hrs. Treatment of mouse marrow cultures with ECF-L increased cox-2 protein expression by 30%.
Conclusion
These results suggest that ECF-L may enhance OCL formation through decreases both in IL-12 and IL-12 receptor expression and that this effect may in part be mediated by increasing cox-2 met
Key Words: ECF-L, Osteoclasts, IL-12
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