Exposure to receptor-activator of NFkappaB ligand renders pre-osteoclasts resistant to IFN-gamma by inducing terminal differentiation.
Exposure to receptor-activator of NFkappaB ligand renders pre-osteoclasts resistant to IFN-gamma by inducing terminal differentiation.
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DOI：
10.1186/ar612
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发表时间：
2003
影响因子：
4.9
通讯作者：
Schwarz EM
中科院分区：
文献类型：
--
作者：
Huang W;O'Keefe RJ;Schwarz EM
虽然已经确定IFN-γ是体外巨噬细胞的强激活剂和破骨细胞生成的有效抑制剂，但还已知该细胞因子在炎性骨丢失的特定情况下产生，例如感染和银屑病关节炎。由于快速IFN-γ巨噬细胞活化（<24小时）和较慢的NFκB配体（RANKL）受体活化剂破骨细胞分化（7天）之间的动力学不同，我们推测IFN-γ对早期和晚期破骨细胞前体具有不同的作用。在RAW264.7细胞和原代脾细胞培养物中，RANKL预处理使这些细胞对最大抗破骨细胞生成剂量的IFN-γ具有抗性。这些细胞也对IFN-γ诱导的一氧化氮产生、形态学变化以及CD 11 B和NFκB受体激活剂的表面上调具有抗性，表明破骨细胞前体早期暴露于RANKL诱导了对IFN-γ细胞效应的广泛抗性。STAT 1激活的变化与这种抵抗无关，因为IFN-γ在早期和晚期破骨细胞前体中同样激活STAT 1。此外，我们未能观察到前破骨细胞中IFN-γ处理后TRAF 6表达的变化。这些数据共同支持了炎性骨丢失模型，其中早期暴露于RANKL可以使用独立于信号分子STAT 1和TRAF 6的机制在高水平IFN-γ存在下引发破骨细胞前体形成。
While it has been established that IFN-γ is a strong activator of macrophages and a potent inhibitor of osteoclastogenesis in vitro, it is also known that this cytokine is produced in particular settings of inflammatory bone loss, such as infection and psoriatic arthritis. Because of the different kinetics between rapid IFN-γ macrophage activation (<24 hours) and the slower receptor-activator of NFκB ligand (RANKL) osteoclast differentiation (7 days), we postulated that IFN-γ would have different effects on early-stage and late-stage osteoclast precursors. In RAW264.7 cells and primary splenocyte cultures, pretreatment with RANKL rendered these cells resistant to maximally anti-osteoclastogenic doses of IFN-γ. These cells were also resistant to IFN-γ-induced nitric oxide production, morphological change, and surface upregulation of CD11b and receptor-activator of NFκB, suggesting that early exposure of osteoclast precursors to RANKL induces a broad resistance to the cellular effects of IFN-γ. Changes in STAT1 activation did not correlate with this resistance, as IFN-γ activated STAT1 equally in both early-stage and late-stage pre-osteoclasts. Furthermore, we failed to observe changes in TRAF6 expression following IFN-γ treatment in pre-osteoclasts. Together these data support a model of inflammatory bone loss in which early exposure to RANKL can prime osteoclast precursors to form in the presence of high levels of IFN-γ using mechanisms independent of the signal molecules STAT1 and TRAF6.
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影响因子：
158.5
作者：
KEY, LL;RODRIGUIZ, RM;RIES, WL
通讯作者：
RIES, WL
DOI：
10.1084/jem.174.3.583
发表时间：
1991-09-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Haanen JB;de Waal Malefijt R;Res PC;Kraakman EM;Ottenhoff TH;de Vries RR;Spits H
通讯作者：
Spits H
DOI：
10.1006/bbrc.2000.3577
发表时间：
2000-10-05
影响因子：
3.1
作者：
Fox, SW;Chambers, TJ
通讯作者：
Chambers, TJ
影响因子：
6.2
作者：
Hong, MH;Williams, H;Pike, JW
通讯作者：
Pike, JW
DOI：
10.1006/bbrc.1999.1623
发表时间：
1999-11-11
影响因子：
3.1
作者：
Horwood, NJ;Kartsogiannis, V;Gillespie, MT
通讯作者：
Gillespie, MT