Primary Human Monocytes Differentiate Into M2 Macrophages And Involve Notch-1 Pathway

Keywords

Atherosclerosis; DAPT; Macrophage; Monocyte; Notch-1; SiRNA

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.

Publication Date

1-1-2016

Publication Title

Canadian Journal of Physiology and Pharmacology

Volume

95

Issue

3

Number of Pages

288-294

Document Type

Article

Personal Identifier

scopus

DOI Link

https://doi.org/10.1139/cjpp-2016-0319

Socpus ID

85014723564 (Scopus)

Source API URL

https://api.elsevier.com/content/abstract/scopus_id/85014723564

This document is currently not available here.

Share

COinS