Title
Regulation of Notch 1 signaling in THP-1 cells enhances M-2 macrophage differentiation
Abbreviated Journal Title
Am. J. Physiol.-Heart Circul. Physiol.
Keywords
Notch 1; monocytes; macrophages; polarization; atherosclerosis; INTERFERON-GAMMA; M2 POLARIZATION; ACTIVATION; EXPRESSION; INFLAMMATION; RECEPTORS; TISSUE; ATHEROSCLEROSIS; INHIBITION; MONOCYTES; Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular; Disease
Abstract
Macrophage polarization is emerging as an important area of research for the development of novel therapeutics to treat inflammatory diseases. Within the current study, the role of Notch1R in macrophage differentiation was investigated as well as downstream effects in THP-1 monocytes cultured in "inflammation mimicry" media. Interference of Notch signaling was achieved using either the pharmaceutical inhibitor DAPT or Notch1R small interfering RNA (siRNA), and Notch1R expression, macrophage phenotypes, and anti-and proinflammatory cytokine expression were evaluated. Data presented show that Notch1R expression on M1 macrophages as well as M-1 macrophage differentiation is significantly elevated during cellular stress (P < 0.05). However, under identical culture conditions, interference to Notch signaling via Notch1R inhibition mitigated these results as well as promoted M-2 macrophage differentiation. Moreover, when subjected to cellular stress, macrophage secretion of proinflammatory cytokines was significantly heightened (P < 0.05). Importantly, Notch1R inhibition not only diminished proinflammatory cytokine secretion but also enhanced anti-inflammatory protein release (P < 0.05). Our data suggest that Notch1R plays a pivotal role in M-1 macrophage differentiation and heightened inflammatory responses. Therefore, we conclude that inhibition of Notch1R and subsequent downstream signaling enhances monocyte to M-2 polarized macrophage outcomes and promotes anti-inflammatory mediation during cellular stress.
Journal Title
American Journal of Physiology-Heart and Circulatory Physiology
Volume
307
Issue/Number
11
Publication Date
1-1-2014
Document Type
Article
Language
English
First Page
H1634
Last Page
H1642
WOS Identifier
ISSN
0363-6135
Recommended Citation
"Regulation of Notch 1 signaling in THP-1 cells enhances M-2 macrophage differentiation" (2014). Faculty Bibliography 2010s. 6095.
https://stars.library.ucf.edu/facultybib2010/6095
Comments
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