The inhibitory effect of interleukin-10 on mouse osteoclast formation involves novel tyrosine-phosphorylated proteins

被引:63
作者
Hong, MH [1 ]
Williams, H [1 ]
Jin, CH [1 ]
Pike, JW [1 ]
机构
[1] Ligand Pharmaceut Inc, Dept Endocrine Res, San Diego, CA 92121 USA
关键词
IL-10; osteoclast; JAK/STATs; signal transduction;
D O I
10.1359/jbmr.2000.15.5.911
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Interleukin-10 (IL-10) inhibits osteoclast (OC) formation in rat and mouse systems, However, little is known concerning the mechanism of this inhibitory effect, Using a coculture system of mouse bone marrow cells and primary osteoblastic cells (POB), we evaluated the potential target cells for IL-IO and components of the IL-10 activating pathway, In the coculture system, IL-10 treatment abolished OC differentiation in a dose-dependent manner, This inhibitory effect occurred regardless of the stage of cellular proliferation and differentiation, suggesting that IL-10 may act on a variety of genes participating in OC formation, IL-10 specifically abrogated the production of IL-6 by enriched bone marrow-derived mononuclear cells (BMM) but not by osteoblastic cells, IL-10 treatment also stimulated the binding of a protein in the BMM to an IL-10 response element, whereas no such activation was induced in osteoblastic cells, In contrast, interferon gamma (IFN-gamma), another inhibitory factor, stimulated tyrosine-phosphorylated proteins to bind to an IL-10 response element in both monocytes and osteoblastic cells, These data suggest that the BMM are the direct target of IL-10 action, Importantly, oligonucleotide-specific precipitation confirmed that IL-10 treatment strongly augmented 88, 85, and 70 kDa tyrosine-phosphorylated proteins in BMM, Taken together, these data show that IL-10 inhibits mouse OC formation by acting directly on hemopoietic OC precursor, through a novel signal transduction and activation pathway.
引用
收藏
页码:911 / 918
页数:8
相关论文
共 38 条
[21]   TRANSCRIPTIONAL RESPONSES TO POLYPEPTIPE LIGANDS - THE JAK-STAT PATHWAY [J].
SCHINDLER, C ;
DARNELL, JE .
ANNUAL REVIEW OF BIOCHEMISTRY, 1995, 64 :621-651
[22]   Osteoprotegerin: A novel secreted protein involved in the regulation of bone density [J].
Simonet, WS ;
Lacey, DL ;
Dunstan, CR ;
Kelley, M ;
Chang, MS ;
Luthy, R ;
Nguyen, HQ ;
Wooden, S ;
Bennett, L ;
Boone, T ;
Shimamoto, G ;
DeRose, M ;
Elliott, R ;
Colombero, A ;
Tan, HL ;
Trail, G ;
Sullivan, J ;
Davy, E ;
Bucay, N ;
RenshawGegg, L ;
Hughes, TM ;
Hill, D ;
Pattison, W ;
Campbell, P ;
Sander, S ;
Van, G ;
Tarpley, J ;
Derby, P ;
Lee, R ;
Boyle, WJ .
CELL, 1997, 89 (02) :309-319
[23]   MODULATION OF OSTEOCLAST DIFFERENTIATION [J].
SUDA, T ;
TAKAHASHI, N ;
MARTIN, TJ .
ENDOCRINE REVIEWS, 1992, 13 (01) :66-80
[24]   Modulation of osteoclast differentiation and function by the new members of the tumor necrosis factor receptor and ligand families [J].
Suda, T ;
Takahashi, N ;
Udagawa, N ;
Jimi, E ;
Gillespie, MT ;
Martin, TJ .
ENDOCRINE REVIEWS, 1999, 20 (03) :345-357
[25]  
TAKAHASHI N, 1986, J IMMUNOL, V137, P3544
[26]   OSTEOBLASTIC CELLS ARE INVOLVED IN OSTEOCLAST FORMATION [J].
TAKAHASHI, N ;
AKATSU, T ;
UDAGAWA, N ;
SASAKI, T ;
YAMAGUCHI, A ;
MOSELEY, JM ;
MARTIN, TJ ;
SUDA, T .
ENDOCRINOLOGY, 1988, 123 (05) :2600-2602
[27]   SOLUBLE INTERLEUKIN-6 RECEPTOR TRIGGERS OSTEOCLAST FORMATION BY INTERLEUKIN-6 [J].
TAMURA, T ;
UDAGAWA, N ;
TAKAHASHI, N ;
MIYAURA, C ;
TANAKA, S ;
YAMADA, Y ;
KOISHIHARA, Y ;
OHSUGI, Y ;
KUMAKI, K ;
TAGA, T ;
KISHIMOTO, T ;
SUDA, T .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1993, 90 (24) :11924-11928
[28]   CYTOKINE SIGNALING THROUGH NONRECEPTOR PROTEIN-TYROSINE KINASES [J].
TANIGUCHI, T .
SCIENCE, 1995, 268 (5208) :251-255
[29]   INTERLEUKIN-10 - A NOVEL STIMULATORY FACTOR FOR MAST-CELLS AND THEIR PROGENITORS [J].
THOMPSONSNIPES, LA ;
DHAR, V ;
BOND, MW ;
MOSMANN, TR ;
MOORE, KW ;
RENNICK, DM .
JOURNAL OF EXPERIMENTAL MEDICINE, 1991, 173 (02) :507-510
[30]   Isolation of a novel cytokine from human fibroblasts that specifically inhibits osteoclastogenesis [J].
Tsuda, E ;
Goto, M ;
Mochizuki, S ;
Yano, K ;
Kobayashi, F ;
Morinaga, T ;
Higashio, K .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1997, 234 (01) :137-142