Microcystin-LR (MC-LR) Triggers Inflammatory Responses in Macrophages.
Microcystin-LR (MC-LR) Triggers Inflammatory Responses in Macrophages.
复制标题
微囊藻毒素-LR（MC - LR）引发巨噬细胞的炎症反应。
DOI：
10.3390/ijms22189939
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发表时间：
2021-09-14
影响因子：
5.6
通讯作者：
Haller ST
中科院分区：
文献类型：
--
作者：
Su RC;Breidenbach JD;Alganem K;Khalaf FK;French BW;Dube P;Malhotra D;McCullumsmith R;Presloid JB;Wooten RM;Kennedy DJ;Haller ST
我们是第一个先前报道微囊藻毒素-LR（MC-LR）在健康小鼠的结肠内具有有限的作用，但在具有预先存在的炎症性肠病的小鼠的结肠内具有毒性作用。在目前的研究中，我们的目的是阐明MC-LR加剧结肠炎的机制，并确定有效的治疗靶点。通过我们目前的调查，我们报告说，有一个显着更大的招聘巨噬细胞进入结肠组织与预先存在的结肠炎的存在下，MC-LR比在没有MC-LR。这通过IHC染色和F4/80阳性巨噬细胞计数以及Cd 68、Cd 11b和Cd 163的基因表达分析定量观察。发现分离的巨噬细胞暴露于MC-LR直接上调巨噬细胞活化标志物Tnf和Illb。通过高通量、无偏的激酶活性分析策略，将MC-LR诱导的磷酸化事件与潜在的抑制剂进行了比较，发现doramapimod可有效预防MC-LR诱导的巨噬细胞炎症反应。
We were the first to previously report that microcystin-LR (MC-LR) has limited effects within the colons of healthy mice but has toxic effects within colons of mice with pre-existing inflammatory bowel disease. In the current investigation, we aimed to elucidate the mechanism by which MC-LR exacerbates colitis and to identify effective therapeutic targets. Through our current investigation, we report that there is a significantly greater recruitment of macrophages into colonic tissue with pre-existing colitis in the presence of MC-LR than in the absence of MC-LR. This is seen quantitatively through IHC staining and the enumeration of F4/80-positive macrophages and through gene expression analysis for Cd68, Cd11b, and Cd163. Exposure of isolated macrophages to MC-LR was found to directly upregulate macrophage activation markers Tnf and Il1b. Through a high-throughput, unbiased kinase activity profiling strategy, MC-LR-induced phosphorylation events were compared with potential inhibitors, and doramapimod was found to effectively prevent MC-LR-induced inflammatory responses in macrophages.
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影响因子：
14.9
作者：
Kuleshov MV;Jones MR;Rouillard AD;Fernandez NF;Duan Q;Wang Z;Koplev S;Jenkins SL;Jagodnik KM;Lachmann A;McDermott MG;Monteiro CD;Gundersen GW;Ma'ayan A
通讯作者：
Ma'ayan A
影响因子：
4.6
作者：
Kubota K;Moriyama M;Furukawa S;Rafiul HASM;Maruse Y;Jinno T;Tanaka A;Ohta M;Ishiguro N;Yamauchi M;Sakamoto M;Maehara T;Hayashida JN;Kawano S;Kiyoshima T;Nakamura S
通讯作者：
Nakamura S
影响因子：
2.8
作者：
Fawell, JK;Mitchell, RE;Hill, RE
通讯作者：
Hill, RE
影响因子：
5
作者：
Chistiakov, Dimitry A.;Killingsworth, Murry C.;Bobryshev, Yuri V.
通讯作者：
Bobryshev, Yuri V.
影响因子：
5.6
作者：
Kennedy DJ;Khalaf FK;Sheehy B;Weber ME;Agatisa-Boyle B;Conic J;Hauser K;Medert CM;Westfall K;Bucur P;Fedorova OV;Bagrov AY;Tang WHW
通讯作者：
Tang WHW