Bone morphogenetic protein 6-induced interleukin-1β expression in macrophages requires PU.1/Smad1 interaction

被引:17
作者
Lee, Geun Taek [1 ,2 ]
Jung, Yeon Suk [1 ,2 ]
Lee, Jae-Ho [1 ,2 ]
Kim, Wun-Jae [3 ]
Kim, Isaac Yi [1 ,2 ]
机构
[1] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Canc Inst New Jersey, Sect Urol Oncol, New Brunswick, NJ 08903 USA
[2] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Canc Inst New Jersey, Dean & Betty Gallo Prostate Canc Ctr, New Brunswick, NJ 08903 USA
[3] Chungbuk Natl Univ, Coll Med, Dept Urol, Cheongju, South Korea
关键词
IL-1; beta; PU.1; Bone morphogenetic protein-6; Macrophages; Cytokines; HUMAN PROINTERLEUKIN-1-BETA; SIGNALING PATHWAYS; CROSS-TALK; TRANSCRIPTION; GENE; DIFFERENTIATION; SEQUENCE; CELLS; SMAD; SPI-1/PU.1;
D O I
10.1016/j.molimm.2011.04.019
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Interleukin 1 beta (IL-1 beta) is a pro-inflammatory cytokine secreted by activated macrophages and monocytes. Previously, we have reported that bone morphogenetic protein-6 (BMP-6) induces inducible nitric oxide synthase (iNOS) expression via IL-1 beta in macrophages. In the present study, we demonstrate that BMP-6 increases IL-1 beta expression in macrophages via the receptors ALK3 and BMPRII as well as the downstream signaling protein Smad1. Surprisingly though, inhibition of the ERK and JNK non-Smad pathways also completely blocked the induction of IL-1 beta by BMP-6 in macrophages. Further analysis revealed that a physical interaction between the transcription factor PU.1 and Smad 1 is necessary for the upregulation of IL-1 beta expression by BMP-6 in macrophages. Taken together, these results demonstrate that BMP-6-induced IL-1 beta expression in macrophages is mediated via a cross-talk between the Smad and the non-Smad pathways through Smad1 and PU.1. (C) 2011 Elsevier Ltd. All rights reserved.
引用
收藏
页码:1540 / 1547
页数:8
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