Syndecan-1 regulates the biological activities of interleukin-34
Syndecan-1 regulates the biological activities of interleukin-34
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DOI：
10.1016/j.bbamcr.2015.01.023
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发表时间：
2015-05-01
影响因子：
5.1
通讯作者：
Heymann, Dominique
中科院分区：
文献类型：
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作者：
Segaliny, Aude I.;Brion, Regis;Heymann, Dominique
IL-34是一种具有挑战性的细胞因子，通过M-CSFR激活与M-CSF共享功能相似性。它还通过与受体蛋白酪氨酸磷酸酶RPTP β /zeta结合，在大脑中发挥着独特的作用，最近得到了解释。本文的目的是寻找IL-34在其他细胞类型上的替代结合。髓系细胞（HL-60、U-937、THP-1）作为M-CSFR的内在表达细胞，M-CSFR在TF-1和HEK293细胞中表达。采用Scatchard和结合抑制实验，使用i -125放射性标记细胞因子和表面等离子体共振研究IL-34的结合。Western blot检测糖胺聚糖磨损、syndecan-1过表达或抑制以及添加阻断性抗syndecan抗体后M-CSFR的活化情况。M-CSF和IL-34诱导M-CSFR磷酸化的不同模式，表明存在IL-34的替代结合。结合实验和软骨素酶处理证实了在缺乏M-CSFR和RPTP β /zeta的细胞上与硫酸软骨素链的低亲和力结合。在具有硫酸软骨素链的蛋白聚糖中，syndecan-1能够调节il -34诱导的M-CSFR信号通路。有趣的是，IL-34诱导了syndecan-1表达细胞的迁移。事实上，IL-34显著增加了THP-1和M2a巨噬细胞的迁移，而添加阻断抗syndecan-1抗体可以抑制THP-1和M2a巨噬细胞的迁移。本文提供了IL-34在细胞表面与硫酸软骨素和syndecan-1的选择性结合，从而调节M-CSFR的激活的证据。此外，il -34诱导的髓细胞迁移是一种syndecan-1依赖性机制。(C) 2015 Elsevier B.V.版权所有
IL-34 is a challenging cytokine sharing functional similarities with M-CSF through M-CSFR activation. It also plays a singular role that has recently been explained in the brain, through a binding to the receptor protein tyrosine phosphatase RPTP beta/zeta. The aim of this paper was to look for alternative binding of IL-34 on other cell types. Myeloid cells (HL-60, U-937, THP-1) were used as cells intrinsically expressing M-CSFR, and M-CSFR was expressed in TF-1 and HEK293 cells. IL-34 binding was studied by Scatchard and binding inhibition assays, using I-125-radiolabelled cytokines, and surface plasmon resonance. M-CSFR activation was analysed by Western blot after glycosaminoglycans abrasion, syndecan-1 overexpression or repression and addition of a blocking anti-syndecan antibody. M-CSF and IL-34 induced different patterns of M-CSFR phosphorylations, suggesting the existence of alternative binding for IL-34. Binding experiments and chondroitinase treatment confirmed low affinity binding to chondroitin sulphate chains on cells lacking both M-CSFR and RPTP beta/zeta. Amongst the proteoglycans with chondroitin sulphate chains, syndecan-1 was able to modulate the IL-34-induced M-CSFR signalling pathways. Interestingly, IL-34 induced the migration of syndecan-1 expressing cells. Indeed, IL-34 significantly increased the migration of THP-1 and M2a macrophages that was inhibited by addition of a blocking anti-syndecan-1 antibody. This paper provides evidence of alternative binding of IL-34 to chondroitin sulphates and syndecan-1 at the cell surface that modulates M-CSFR activation. In addition, IL-34-induced myeloid cell migration is a syndecan-1 dependent mechanism. (C) 2015 Elsevier B.V. All rights reserved.