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BMC Res Notes. 2019 Apr 22;12(1):234. doi: 10.1186/s13104-019-4273-5.

Mebendazole-induced M1 polarisation of THP-1 macrophages may involve DYRK1B inhibition.

Author information

1
Department of Medical Sciences, Division of Cancer Pharmacology and Computational Medicine, Uppsala University, 75185, Uppsala, Sweden.
2
Department of Immunology, Genetics and Pathology, Uppsala University, 75185, Uppsala, Sweden.
3
Department of Medical Sciences, Division of Cancer Pharmacology and Computational Medicine, Uppsala University, 75185, Uppsala, Sweden. rolf.larsson@medsci.uu.se.

Abstract

OBJECTIVE:

We recently showed that the anti-helminthic compound mebendazole (MBZ) has immunomodulating activity by inducing a M2 to M1 phenotype switch in monocyte/macrophage models. In the present study we investigated the potential role of protein kinases in mediating this effect.

RESULTS:

MBZ potently binds and inhibits Dual specificity tyrosine-phosphorylation-regulated kinase 1B (DYRK1B) with a Kd and an IC50 of 7 and 360 nM, respectively. The specific DYRK1B inhibitor AZ191 did not mimic the cytokine release profile of MBZ in untreated THP-1 monocytes. However, in THP-1 cells differentiated into macrophages, AZ191 strongly induced a pro-inflammatory cytokine release pattern similar to MBZ and LPS/IFNγ. Furthermore, like MBZ, AZ191 increased the expression of the M1 marker CD80 and decreased the M2 marker CD163 in THP-1 macrophages. In this model, AZ191 also increased phospho-ERK activity although to a lesser extent compared to MBZ. Taken together, the results demonstrate that DYRK1B inhibition could, at least partly, recapitulate immune responses induced by MBZ. Hence, DYRK1B inhibition induced by MBZ may be part of the mechanism of action to switch M2 to M1 macrophages.

KEYWORDS:

DYRK1B; M1 polarisation; Mebendazole; Monocytes and macrophages

PMID:
31010428
PMCID:
PMC6477744
DOI:
10.1186/s13104-019-4273-5
[Indexed for MEDLINE]
Free PMC Article

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