Reducing Suppressors of Cytokine Signaling-3 (SOCS3) Expression Promotes M2 Macrophage Polarization and Functional Recovery After Intracerebral Hemorrhage.
Reducing Suppressors of Cytokine Signaling-3 (SOCS3) Expression Promotes M2 Macrophage Polarization and Functional Recovery After Intracerebral Hemorrhage.
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DOI：
10.3389/fneur.2020.586905
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发表时间：
2020
影响因子：
3.4
通讯作者：
Zhao G
中科院分区：
文献类型：
--
作者：
Ji XC;Shi YJ;Zhang Y;Chang MZ;Zhao G
脑出血（ICH）是一种致死性卒中亚型，目前仍缺乏有效的干预措施来改善其功能结局。细胞因子信号转导抑制因子3（SOCS 3）通过负性调节细胞因子-Jak-Stat信号转导在炎症反应中起关键作用。然而，SOCS 3在巨噬细胞极化调节中的作用存在很大争议，SOCS 3的精细调节需要进一步了解。本研究通过尾状核注射胶原酶建立大鼠脑出血模型。为了减少出血性病变区域中小胶质细胞/巨噬细胞中的SOCS 3表达，我们在ICH后24小时将慢病毒短发夹RNA（shSOCS 3）（Lenti-shSOCS 3）注射到血肿腔中。我们发现，与Lenti-EGFP和生理盐水组相比，在接受Lenti-shSOCS 3注射的动物中，iNOS阳性细胞（M1表型）的数量显著减少，而抗氧化酶-1阳性细胞（M2表型）显著升高。促炎酶-1阳性细胞的增加与促炎微环境显著降低相关，包括促炎细胞因子[白细胞介素（IL）-1β、IL-6和TNF-α]的下调和抗炎（IL-10）介质的同时上调。此外，这种向M2表型的显著转变与抑制NF-κB活化相关。此外，这些变化显著增强了Lenti-shSOCS 3注射动物的神经保护作用和功能恢复。我们的研究结果表明，SOCS 3表达的减少导致了M2表型的明显偏向，并改善了炎症微环境，这增强了神经保护作用，并导致ICH后功能恢复的显着改善。
Intracerebral hemorrhage (ICH) is a fatal subtype of stroke, and effective interventions to improve the functional outcomes are still lacking. Suppressor of cytokine signaling 3 (SOCS3) plays critical roles in the inflammatory response by negatively regulating cytokine-Jak–Stat signaling. However, the role of SOCS3 in the regulation of macrophage polarization is highly controversial and the fine regulation exerted by SOCS3 needs further understanding. In this study, rat ICH models were established by infusion of collagenase into the caudate nucleus. To decrease SOCS3 expression into microglia/macrophages in the hemorrhagic lesion area, we injected lentiviral short hairpin RNA (shSOCS3) (Lenti-shSOCS3) into the hematoma cavity at 24 h following ICH. We found that the number of iNOS-positive cells (M1 phenotype) was significantly reduced, whereas arginase-1-positive cells (M2 phenotype) were markedly elevated in animals that received Lenti-shSOCS3 injections compared with those in the Lenti-EGFP and saline groups. The increase in arginase-1-positive cells was associated with a significantly lower pro-inflammatory microenvironment, which included the downregulation of pro-inflammatory cytokines [interleukin (IL)-1β, IL-6, and TNF-α] and concurrent upregulation of anti-inflammatory (IL-10) mediators. In addition, this marked shift toward the M2 phenotype was associated with suppressed NF-κB activation. Furthermore, these changes notably enhanced the neuroprotective effects and functional recovery in Lenti-shSOCS3-injected animals. Our findings indicated that reduction in SOCS3 expression caused a marked bias toward the M2 phenotype and ameliorated the inflammatory microenvironment, which enhanced neuroprotective effects and resulted in notable improvement in functional recovery after ICH.
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影响因子：
6.7
作者：
Carow B;Reuschl AK;Gavier-Widén D;Jenkins BJ;Ernst M;Yoshimura A;Chambers BJ;Rottenberg ME
通讯作者：
Rottenberg ME
影响因子：
15.1
作者：
Liu, Jingjin;Nolte, Kay;Coburn, Mark
通讯作者：
Coburn, Mark
DOI：
10.1056/nejmoa1700554
发表时间：
2017-10-26
期刊：
The New England journal of medicine
影响因子：
--
作者：
Eichler F;Duncan C;Musolino PL;Orchard PJ;De Oliveira S;Thrasher AJ;Armant M;Dansereau C;Lund TC;Miller WP;Raymond GV;Sankar R;Shah AJ;Sevin C;Gaspar HB;Gissen P;Amartino H;Bratkovic D;Smith NJC;Paker AM;Shamir E;O'Meara T;Davidson D;Aubourg P;Williams DA
通讯作者：
Williams DA
褪黑激素通过 STAT3 通路调节小胶质细胞/巨噬细胞极化至抗炎表型，从而预防缺血性中风
影响因子：
5.5
作者：
Liu, Zong-Jian;Ran, Yuan-Yuan;Xi, Jia-Ning
通讯作者：
Xi, Jia-Ning
影响因子：
17.1
作者：
Brentjens RJ;Davila ML;Riviere I;Park J;Wang X;Cowell LG;Bartido S;Stefanski J;Taylor C;Olszewska M;Borquez-Ojeda O;Qu J;Wasielewska T;He Q;Bernal Y;Rijo IV;Hedvat C;Kobos R;Curran K;Steinherz P;Jurcic J;Rosenblat T;Maslak P;Frattini M;Sadelain M
通讯作者：
Sadelain M