| First Author | Su RC | Year | 2021 |
| Journal | Int J Mol Sci | Volume | 22 |
| Issue | 18 | PubMed ID | 34576099 |
| Mgi Jnum | J:313713 | Mgi Id | MGI:6766197 |
| Doi | 10.3390/ijms22189939 | Citation | Su RC, et al. (2021) Microcystin-LR (MC-LR) Triggers Inflammatory Responses in Macrophages. Int J Mol Sci 22(18) |
| abstractText | 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. |
