| 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 |
|
PDF Links
Full text via DOI
Download Citation
