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Microcystin-LR (MC-LR) Triggers Inflammatory Responses in Macrophages
- Source :
- International Journal of Molecular Sciences, Vol 22, Iss 18, p 9939 (2021)
- Publication Year :
- 2021
- Publisher :
- MDPI AG, 2021.
-
Abstract
- 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.
- Subjects :
- microcystin
colitis
macrophages
Biology (General)
QH301-705.5
Chemistry
QD1-999
Subjects
Details
- Language :
- English
- ISSN :
- 22189939, 14220067, and 16616596
- Volume :
- 22
- Issue :
- 18
- Database :
- Directory of Open Access Journals
- Journal :
- International Journal of Molecular Sciences
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.3155eb4fe2a846e3a19e8f384b6dd915
- Document Type :
- article
- Full Text :
- https://doi.org/10.3390/ijms22189939