Cytochrome P450 1A1 enhances inflammatory responses and impedes phagocytosis of bacteria in macrophages during sepsis
Cytochrome P450 1A1 enhances inflammatory responses and impedes phagocytosis of bacteria in macrophages during sepsis
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脓毒症期间细胞色素 P450 1A1 增强炎症反应并阻碍巨噬细胞对细菌的吞噬作用
DOI：
10.1186/s12964-020-0523-3
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发表时间：
2020-05
影响因子：
8.4
通讯作者：
Liang Hua-Ping
中科院分区：
文献类型：
--
作者：
Tian Li-Xing;Tang Xin;Zhu Jun-Yu;Luo Li;Ma Xiao-Yuan;Cheng Shao-Wen;Zhang Wei;Tang Wan-Qi;Ma Wei;Yang Xue;Lv Chuan-Zhu;Liang Hua-Ping
摘要细胞色素P450 1A 1（CYP 1A 1）是由炎症限制性芳烃受体（AhR）调节的，但CYP 1A 1的免疫功能尚不清楚。我们观察到CYP 1A 1在LPS或热灭活大肠杆菌后小鼠腹腔巨噬细胞（PMs）中的过度表达。coli（E. coli）攻毒。CYP 1A 1过表达可通过增强JNK/AP-1信号通路增加RAW 264.7细胞（RAW）TNF-α和IL-6的产生。CYP 1A 1过表达还促进活化RAW中12 S-羟基-5Z，8 Z，10 E，14 Z-二十碳四烯酸（12（S）-HETE）的产生，而12（S）-HETE抗体减弱和12（S）-HETE单独诱导炎症反应。含有羟化酶缺陷型CYP 1A 1的巨噬细胞显示12（S）-HETE生成和LPS诱导的TNF-α/IL-6分泌减少。CYP 1A 1过表达还通过降低PMs中清道夫受体A（SR-A）的表达而损害细菌的吞噬作用。注射过表达CYP 1A 1的PM的小鼠对CLP或E更敏感。大肠杆菌诱导的死亡率和细菌入侵，而漏芦，一种选择性CYP 1A 1抑制剂，提高败血症小鼠的生存和细菌清除。脓毒症患者单核细胞和血浆中的CYP 1A 1和12（S）-HETE也升高，并与SOFA评分呈正相关。巨噬细胞CYP 1A 1破坏可能是治疗脓毒症的一种有前途的策略。
AbstractThe hydroxylase cytochrome P450 1A1 (CYP1A1) is regulated by the inflammation-limiting aryl hydrocarbon receptor (AhR), but CYP1A1 immune functions remain unclear. We observed CYP1A1 overexpression in peritoneal macrophages (PMs) isolated from mice following LPS or heat-killedEscherichia. coli(E. coli) challenge. CYP1A1 overexpression augmented TNF-α and IL-6 production in RAW264.7 cells (RAW) by enhancing JNK/AP-1 signalling. CYP1A1 overexpression also promoted 12S-hydroxy-5Z,8Z,10E,14Z-eicosatetraenoic acid (12(S)-HETE) production in activated RAW, while a 12(S)-HETE antibody attenuated and 12(S)-HETE alone induced inflammatory responses. Macrophages harbouring hydroxylase-deficient CYP1A1 demonstrated reduced 12(S)-HETE generation and LPS-induced TNF-α/IL-6 secretion. CYP1A1 overexpression also impaired phagocytosis of bacteria via decreasing the expression of scavenger receptor A (SR-A) in PMs. Mice injected with CYP1A1-overexpressing PMs were more susceptible to CLP- orE. coli-induced mortality and bacteria invading, while Rhapontigenin, a selective CYP1A1 inhibitor, improved survival and bacteria clearance of mice in sepsis. CYP1A1 and 12(S)-HETE were also elevated in monocytes and plasma of septic patients and positively correlated with SOFA scores. Macrophage CYP1A1 disruption could be a promising strategy for treating sepsis.Video abstractGraphical abstract
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影响因子：
5.3
作者：
通讯作者：
--
DOI：
--
发表时间：
1994-10
期刊：
Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research
影响因子：
--
作者：
T. Lysz;J. Arora;C. Lin;P. Zelenka
通讯作者：
T. Lysz;J. Arora;C. Lin;P. Zelenka
影响因子：
5
作者：
Deng Y;Theken KN;Lee CR
通讯作者：
Lee CR
DOI：
10.4049/jimmunol.1300699
发表时间：
2013-09-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Divanovic S;Dalli J;Jorge-Nebert LF;Flick LM;Gálvez-Peralta M;Boespflug ND;Stankiewicz TE;Fitzgerald JM;Somarathna M;Karp CL;Serhan CN;Nebert DW
通讯作者：
Nebert DW
影响因子：
3.8
作者：
A. Hoffer;Ching-yi Chang;Alvaro Puga
通讯作者：
A. Hoffer;Ching-yi Chang;Alvaro Puga