Apoptotic cell-derived factors induce arginase II expression in murine macrophages by activating ERK5/CREB
Apoptotic cell-derived factors induce arginase II expression in murine macrophages by activating ERK5/CREB
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DOI：
10.1007/s00018-010-0537-x
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发表时间：
2011-05-01
影响因子：
8
通讯作者：
Bruene, Bernhard
中科院分区：
文献类型：
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作者：
Barra, Vera;Kuhn, Anne-Marie;Bruene, Bernhard
凋亡细胞（AC）衍生因子改变巨噬细胞（MI打破垂直栏）的生理学朝向调节表型，其特征在于减少一氧化氮（NO）的产生。受损的NO形成AC-条件培养基（CM）的促进，由精氨酸酶II（ARG II）的表达，竞争诱导型NO合成酶的L-精氨酸。在这里，我们探讨了允许CM上调RAW 264.7 MI断裂垂直条中ARG II的信号通路。鞘氨醇-1-磷酸（S1 P）是必需的，并与一个迄今尚未确定的因子协同作用，以引起高ARG II表达。S1 P激活S1 P（2），因为S1 P（2）敲低阻止ARG II上调。此外，ERK 5敲低减弱CM介导的ARG II蛋白诱导。EMSA分析和诱饵寡核苷酸清除RAW264.7MI断裂垂直条中的CREB，其阻断ARG II表达，表明CREB参与。我们的结论是AC衍生的S1 P与S1 P结合（2），并与其他因子协同激活ERK 5和CREB。该信号级联通过ARG II诱导形成抗炎性MI破竖条表型。
Apoptotic cell (AC)-derived factors alter the physiology of macrophages (MI broken vertical bar s) towards a regulatory phenotype, characterized by reduced nitric oxide (NO) production. Impaired NO formation in response to AC-conditioned medium (CM) was facilitated by arginase II (ARG II) expression, which competes with inducible NO synthase for l-arginine. Here we explored signaling pathways allowing CM to upregulate ARG II in RAW264.7 MI broken vertical bar s. Sphingosine-1-phosphate (S1P) was required and acted synergistically with a so far unidentified factor to elicit high ARG II expression. S1P activated S1P(2), since S1P(2) knockdown prevented ARG II upregulation. Furthermore, ERK5 knockdown attenuated CM-mediated ARG II protein induction. CREB was implicated as shown by EMSA analysis and decoy-oligonucleotides scavenging CREB in RAW264.7 MI broken vertical bar s, which blocked ARG II expression. We conclude that AC-derived S1P binds to S1P(2) and acts synergistically with other factors to activate ERK5 and concomitantly CREB. This signaling cascade shapes an anti-inflammatory MI broken vertical bar phenotype by ARG II induction.