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Nlrp3, Csf3, and Edn1 in Macrophage Response to Saturated Fatty Acids and Modified Low-Density Lipoprotein

 Youk, Harin  ;  Kim, Miso  ;  Lee, Chan Joo  ;  Oh, Jaewon  ;  Park, Sungha  ;  Kang, Seok-Min  ;  Kim, Jeong-Ho  ;  Ann, Soo-jin  ;  Lee, Sang-Hak 
 KOREAN CIRCULATION JOURNAL, Vol.51(1) : 68-80, 2021-01 
Journal Title
Issue Date
Atherosclerosis ; Metabolic syndrome ; Immunity ; Obesity
Background and Objectives: The relationship between metabolic stress, inflammation, and cardiovascular disease is being studied steadily. The aim of this study was to evaluate the effect of palmitate (PA) and minimally modified low-density lipoprotein (mmLDL) on macrophages and to identify the associated pathways. Methods: J774 macrophages were incubated with PA or mmLDL and lipopolysaccharide (LPS). Secretion of inflammatory chemokines and the expression of corresponding genes were determined. The phosphorylation of extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase was also assessed. RNA sequencing of macrophages was performed to identify the genes regulated by PA or mmLDL. Some of the genes regulated by the 2 agents were validated by knocking down the cells using small interfering RNA. Results: PA or mmLDL promoted the secretion of interleukin (IL)-6 and IL-1 beta in LPS-stimulated macrophages, and this was accompanied by higher phosphorylation of ERK. RNA sequencing revealed dozens of genes that were regulated in this process, such as Csf3and Edn1, which were affected by PA and mmLDL, respectively. These agents also increased NIrp3 expression. The effect of Csf3 or Edn1 silencing on inflammation was modest, whereas toll-like receptor (TLR) 4 inhibition reduced a large proportion of macrophage activation. Conclusions: We demonstrated that the proinflammatory milieu with high levels of PA or mmLDL promoted macrophage activation and the expression of associated genes such as NIrp3, 613, and Edn1. Although the TLR4 pathway appeared to be most relevant, additional role of other genes in this process provided insights regarding the potential targets for intervention.
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Laboratory Medicine (진단검사의학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Research Institute (부설연구소) > 1. Journal Papers
Yonsei Authors
Kang, Seok Min(강석민) ORCID logo https://orcid.org/0000-0001-9856-9227
Kim, Jeong Ho(김정호) ORCID logo https://orcid.org/0000-0003-2479-0548
Park, Sung Ha(박성하) ORCID logo https://orcid.org/0000-0001-5362-478X
Ann, Soo Jin(안수진)
Oh, Jae Won(오재원) ORCID logo https://orcid.org/0000-0002-4585-1488
Lee, Sang Hak(이상학) ORCID logo https://orcid.org/0000-0002-4535-3745
Lee, Chan Joo(이찬주) ORCID logo https://orcid.org/0000-0002-8756-409X
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