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Microcystin-LR (MC-LR) Triggers Inflammatory Responses in Macrophages

Department of Medicine, The University of Toledo College of Medicine and Life Sciences, Toledo, OH 43614, USA
Department of Neuroscience, The University of Toledo College of Medicine and Life Sciences, Toledo, OH 43614, USA
Neurosciences Center, Promedica, Toledo, OH 43614, USA
Department of Medical Microbiology and Immunology, The University of Toledo College of Medicine and Life Sciences, Toledo, OH 43614, USA
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editor: Guido R. M. M. Haenen
Int. J. Mol. Sci. 2021, 22(18), 9939;
Received: 25 May 2021 / Revised: 31 August 2021 / Accepted: 8 September 2021 / Published: 14 September 2021
(This article belongs to the Collection Feature Papers in Molecular Toxicology)
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. View Full-Text
Keywords: microcystin; colitis; macrophages microcystin; colitis; macrophages
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MDPI and ACS Style

Su, R.C.; Breidenbach, J.D.; Alganem, K.; Khalaf, F.K.; French, B.W.; Dube, P.; Malhotra, D.; McCullumsmith, R.; Presloid, J.B.; Wooten, R.M.; Kennedy, D.J.; Haller, S.T. Microcystin-LR (MC-LR) Triggers Inflammatory Responses in Macrophages. Int. J. Mol. Sci. 2021, 22, 9939.

AMA Style

Su RC, Breidenbach JD, Alganem K, Khalaf FK, French BW, Dube P, Malhotra D, McCullumsmith R, Presloid JB, Wooten RM, Kennedy DJ, Haller ST. Microcystin-LR (MC-LR) Triggers Inflammatory Responses in Macrophages. International Journal of Molecular Sciences. 2021; 22(18):9939.

Chicago/Turabian Style

Su, Robin C., Joshua D. Breidenbach, Khaled Alganem, Fatimah K. Khalaf, Benjamin W. French, Prabhatchandra Dube, Deepak Malhotra, Robert McCullumsmith, John B. Presloid, R. M. Wooten, David J. Kennedy, and Steven T. Haller 2021. "Microcystin-LR (MC-LR) Triggers Inflammatory Responses in Macrophages" International Journal of Molecular Sciences 22, no. 18: 9939.

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