Ubiquitin-like protein MNSFβ/endophilin II complex regulates Dectin-1-mediated phagocytosis and inflammatory responses in macrophages
Ubiquitin-like protein MNSFβ/endophilin II complex regulates Dectin-1-mediated phagocytosis and inflammatory responses in macrophages
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DOI：
10.1016/j.bbrc.2010.09.045
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发表时间：
2010-10-15
影响因子：
3.1
通讯作者：
Watanabe, Natsuko
中科院分区：
文献类型：
--
作者：
Nakamura, Morihiko;Watanabe, Natsuko
单克隆非特异性抑制因子β（MNSF β）的翻译后修饰涉及多种细胞事件的调节。先前的研究已经证明，MNSF β共价结合到巨噬细胞系Raw 264.7中的细胞内促凋亡蛋白Bcl-G，表明这种泛素样蛋白参与了细胞凋亡。最近，我们发现MNSF β共价结合到内亲和素II，内亲和素A家族的成员，并抑制巨噬细胞的吞噬作用。在这项研究中，我们进一步研究了MNSF β/endophilin II复合物在酵母多糖吞噬作用中的作用机制。MNSF beta/endophilin II I介导的对Raw 264.7细胞中吞噬作用的抑制被抗Decti-1 β-葡聚糖受体mAb中和，表明MNSF beta/endophilin II是调节吞噬作用的Dectin-1信号传导的介质。β-葡聚糖依赖性TNF α对酵母聚糖的反应通过用内亲和素II siRNA和/或MNSF β siRNA处理而显著增加。相反，共转染的endophilin II和MNSF β cDNA抑制酵母多糖诱导的TNF α的生产的增强。有趣的是，endophilin II siRNA不影响Pam（3）CSK（4）（TLR 2特异性配体）诱导的TNF α产生。Endophilin II和/或MNSF β siRNA增强酵母多糖诱导的I κ β α降解。总之，这些结果表明，MNSF β/endophilin II抑制IKK激活上游的信号通路，但不抑制TLR 2信号传导的下游。(C)2010年爱思唯尔公司All rights reserved.
Post-translational modification by monoclonal nonspecific suppressor factor beta (MNSF beta) has been implicated in the regulation of a variety of cellular events. Previous studies have demonstrated that MNSF beta covalently binds to the intracellular pro-apoptotic protein Bcl-G in a macrophage cell line, Raw264.7, suggesting involvement of this ubiquitin-like protein in apoptosis. Most recently, we found that MNSF beta covalently conjugates to endophilin II, a member of the endophilin A family, and inhibits phagocytosis by macrophages. In this study, we further examined the mechanism of action of MNSF beta/endophilin II complex in the phagocytosis of zymosan. MNSF beta/endophilin II I mediated inhibition of phagocytosis in Raw264.7 cells was neutralized by anti-Decti-1, beta-glucan receptor, mAb, indicating that MNSF beta/endophilin II is a mediator of Dectin-1 signaling in regulating phagocytosis. The beta-glucan-dependent TNF alpha response to zymosan was significantly increased by the treatment with endophilin II siRNA and/or MNSF beta siRNA. Conversely, cotransfection of endophilin II and MNSF beta cDNAs inhibited the enhancement of zymosan-induced TNF alpha production. Interestingly, endophilin II siRNA did not affect Pam(3)CSK(4) (TLR2 specific ligand)-induced TNF alpha production. Endophilin II and/or MNSF beta siRNA enhanced zymosan-induced I kappa beta alpha degradation. Together, these results demonstrate that MNSF beta/endophilin II inhibits the signal path-way upstream of IKK activation, but not downstream of TLR2 signaling. (C) 2010 Elsevier Inc. All rights reserved.