HDAC10 alleviates inflammation after intracerebral hemorrhage via the PTPN22/NLRP3 pathway in rats
HDAC10 alleviates inflammation after intracerebral hemorrhage via the PTPN22/NLRP3 pathway in rats
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HDAC10通过PTPN22/NLRP3通路减轻大鼠脑出血后的炎症
DOI：
10.1016/j.neuroscience.2020.02.027
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发表时间：
2020
期刊：
影响因子：
3.3
通讯作者：
赵敬
中科院分区：
文献类型：
--
作者：
赵敬
含有吡咯结构域的3个炎症体(NLRP3)是NOD样受体家族的成员，在脑出血(ICH)所致损伤的炎症过程中起着重要作用。组蛋白脱乙酰酶10(HDAC10)是新近发现的一种参与免疫反应的组蛋白II类脱乙酰酶。然而，HDAC10如何影响脑出血后的炎症反应仍不清楚。在这项研究中，我们研究了HDAC10是否通过蛋白酪氨酸磷酸酶-非受体类型22(PTPN22)途径抑制NLRP3炎症小体的激活来减轻ICH损伤。我们用单次输注自体血的方法诱导SD大鼠(健康的，成年的雄性)脑出血。为了敲除HDAC10，我们将siRNA注射到大鼠体内。为了进一步探讨HDAC10在脑出血损伤中的作用机制，PTPN22被沉默。人和大鼠脑出血后HDAC10水平均升高，并于脑出血后24小时达高峰。抑制HDAC10基因表达可加重脑出血损伤，表现为神经功能评分、脑含水量、伊文思蓝渗出、髓过氧化物酶(MPO)细胞数、尼氏染色和HE染色结果。此外，HDAC10基因敲除可增加PTPN22的表达，加重NLRP3炎症小体介导的炎症反应。HDAC10沉默增加。NLRP3炎症体激活，这可被使用siRNA的PTPN22基因敲除有效逆转。此外，HDAC10沉默还促进了PTPN22和NLRP3的相互作用。我们的研究表明，HDAC10沉默通过PTPN22途径加重了NLRP3介导的大鼠脑出血后的炎症反应。这些结果提示，调节NLRP3炎症小体可能是减轻脑出血损伤的一种新方法。
Pyrin domain-containing 3 inflammasome (NLRP3), a member of the NOD-like receptor.family, has a crucial role in the inflammatory process that occurs during intracerebral hemorrhage.(ICH)-induced injury. Histone deacetylase 10 (HDAC10) is a newly identified class II histone.deacetylase involved in immune responses. However, how HDAC10 affects the inflammatory.response after ICH remains unknown. In this study, we investigated whether HDAC10 relieves ICH.injury by suppressing NLRP3 inflammasome activation through the protein tyrosine phosphatase,.nonreceptor type 22 (PTPN22) pathway. We induced ICH in Sprague-Dawley rats (healthy, male.adult) with a single infusion of autologous blood. To knockdown HDAC10, we injected siRNA into.the rats. To further explore the mechanisms underlying the role of HDAC10 in ICH injury, PTPN22.was silenced. HDAC10 levels were upregulated after ICH in humans and rats, and reached peak.levels 24 h after ICH induction in rats. HDAC10 silencing aggravated ICH injury, as demonstrated.by increased modified neurological severity scores, brain water content, Evans blue extravasation,.and number of myeloperoxidase (MPO) cells, and the results of Nissl and H&E staining..Furthermore, HDAC10 knockdown increased the expression of PTPN22 and accentuated.inflammatory responses mediated by the NLRP3 inflammasome. HDAC10 silencing increased.NLRP3 inflammasome activation, and this was effectively reversed by PTPN22 knockdown using.siRNA. Furthermore, HDAC10 silencing also promoted the interaction of PTPN22 and NLRP3..Our study demonstrated that HDAC10 silencing aggravated NLRP3-mediated inflammatory.responses after ICH in rats via the PTPN22 pathway. These results suggest that regulating the.NLRP3 inflammasome may be a novel method to ameliorate ICH injury.
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影响因子：
5.3
作者：
Yang X;Sun J;Kim TJ;Kim YJ;Ko SB;Kim CK;Jia X;Yoon BW
通讯作者：
Yoon BW
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影响因子：
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作者：
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影响因子：
13.3
作者：
Spalinger MR;Lang S;Gottier C;Dai X;Rawlings DJ;Chan AC;Rogler G;Scharl M
通讯作者：
Scharl M
影响因子：
32.4
作者：
Wang Y;Shaked I;Stanford SM;Zhou W;Curtsinger JM;Mikulski Z;Shaheen ZR;Cheng G;Sawatzke K;Campbell AM;Auger JL;Bilgic H;Shoyama FM;Schmeling DO;Balfour HH Jr;Hasegawa K;Chan AC;Corbett JA;Binstadt BA;Mescher MF;Ley K;Bottini N;Peterson EJ
通讯作者：
Peterson EJ
影响因子：
7.4
作者：
Diaz-Gallo LM;Espino-Paisán L;Fransen K;Gómez-García M;van Sommeren S;Cardeña C;Rodrigo L;Mendoza JL;Taxonera C;Nieto A;Alcain G;Cueto I;López-Nevot MA;Bottini N;Barclay ML;Crusius JB;van Bodegraven AA;Wijmenga C;Ponsioen CY;Gearry RB;Roberts RL;Weersma RK;Urcelay E;Merriman TR;Alizadeh BZ;Martin J
通讯作者：
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