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Microcystin-LR (MC-LR) Triggers Inflammatory Responses in Macrophages
oleh: Robin C. Su, Joshua D. Breidenbach, Khaled Alganem, Fatimah K. Khalaf, Benjamin W. French, Prabhatchandra Dube, Deepak Malhotra, Robert McCullumsmith, John B. Presloid, R. Mark Wooten, David J. Kennedy, Steven T. Haller
Format: | Article |
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Diterbitkan: | MDPI AG 2021-09-01 |
Deskripsi
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 <i>Cd68</i>, <i>Cd11b</i>, and <i>Cd163</i>. Exposure of isolated macrophages to MC-LR was found to directly upregulate macrophage activation markers <i>Tnf</i> and <i>Il1b</i>. 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.