Primary human monocytes differentiate into M2 macrophages and involve Notch-1 pathway - PubMed (original) (raw)

. 2017 Mar;95(3):288-294.

doi: 10.1139/cjpp-2016-0319. Epub 2017 Feb 25.

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Primary human monocytes differentiate into M2 macrophages and involve Notch-1 pathway

Dinender K Singla et al. Can J Physiol Pharmacol. 2017 Mar.

Abstract

The current study investigates whether inhibiting the Notch-1 signaling pathway in primary human monocytes enhances M2 macrophage differentiation. We generated a primary human monocyte cell culture model to understand the effect of the Notch-1 signaling pathway. Monocytes were treated with Notch-1 inhibitors DAPT or siRNA. Our data show that there was a significant increase in the M1 macrophage population demonstrated by iNOS marker in the primary human monocytes treated with apoptotic-conditioned medium (ACM). Next, the levels of pro-inflammatory cytokines IL-6 and MCP-1, as well as TNF-α, increased in ACM media (p < 0.05). Furthermore, M1 macrophages and pro-inflammatory cytokines were reduced following DAPT or siRNA treatment. Comparatively, there was a significant increase in M2 macrophages, as demonstrated by an increase in CD206 and arginase-1 positive cells treated with DAPT or siRNA (p < 0.05). Furthermore, a significant increase in the associated anti-inflammatory cytokines IL-10 and IL-1RA was also observed with respect to control groups (p < 0.05). We conclude that blocking the Notch-1 pathway with DAPT or siRNA attenuates pro-inflammatory cytokines, enhances M2 macrophage differentiation, and increases anti-inflammatory cytokines in primary human monocytes. As a result, Notch-1 pathway inhibition has potential therapeutic applications of inflammatory disease.

Keywords: ARN interférent; DAPT; Notch-1; atherosclerosis; athérosclérose; macrophage; monocyte; siRNA.

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