|
KMID : 0438420070140020141
|
|
Korean Journal of Bone Metabolism
2007 Volume.14 No. 2 p.141 ~ p.147
|
|
|
Eosinophil Chemotactic Factor-L (ECF-L) Blocks The Suppressive Effects of IL-12 On Osteoclast Formation
|
|
Chung Ho-Yeon
|
|
|
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 metabolites such as PGE2. [Korean Journal of Bone Metabolism, 14(2): 141-147, 2007]
|
|
|
KEYWORD
|
|
|
ECF-L, Osteoclasts, IL-12
|
|
|
FullTexts / Linksout information
|
|
|
|
|
|
Listed journal information
|
|
 
|
|