The Effects of Discoidin Domain Receptor 1 on Macrophage Phenotype in Vascular Inflammatory Disease
Year: 2015
Type: dissertation
Abstract: In atherosclerosis, the expression of discoidin domain receptor 1 (DDR1) promotes macrophage accumulation in the arterial vessel wall in hyper-cholesterolemic mice; however, the mechanism involved remains elusive. DDR1 has been hypothesized to enhance macrophage accumulation by mediating the phenotypic polarization of these leukocytes. We report here that DDR1-expressing and DDR1-null macrophages displayed incongruent cytokine profiles in the in vivo plaque. In vitro, DDR1 blunted the up-regulation of anti-inflammatory genes in peritoneal macrophages following IL-4 stimulation. Moreover, DDR1 correlated with a relative decrease in the mRNA expression of select MMPs and TIMP-2, suggestive of a reduced matrix remodeling efficiency that may contribute to accelerated plaque expansion. Our findings preliminarily demonstrate that DDR1 effects an overall pro-inflammatory status in macrophages by dampening their adaptability to anti-inflammatory stimuli. Further effort to determine how DDR1 fine-tunes macrophage polarization will be relevant to the engineering of effective treatment for atherosclerosis and other inflammatory diseases.
Source: TSpace (University of Toronto)
Author: Winnie Cheuk-Yan Fung
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2564997350