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Palmitate and minimally-modified low-density lipoprotein cooperatively promote inflammatory responses in macrophages

 Soo-Jin Ann  ;  Ka-Kyung Kim  ;  Eun Jeong Cheon  ;  Hye-Min Noh  ;  Inhwa Hwang  ;  Je-Wook Yu  ;  Sungha Park  ;  Seok-Min Kang  ;  Ichiro Manabe  ;  Yury I Miller  ;  Sangwoo Kim  ;  Sang-Hak Lee 
 PLOS ONE, Vol.13(3) : e0193649, 2018 
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Animals ; CD36 Antigens/metabolism ; Cell Line ; Cytokines/secretion ; Drug Dose-Response Relationship ; Drug Synergism ; Escherichia coli ; Gene Expression/drug effects ; Humans ; Immunologic Factors/*pharmacology ; Lipopolysaccharides/*pharmacology ; LDL/metabolism/*pharmacology Lipoproteins ; MAP Kinase Signaling System/drug effects ; Macrophages/*drug effects/*immunology ; Mice ; Palmitates/*pharmacology ; Class E/metabolism Scavenger Receptors
Increased consumption of Western-type diets and environmental insults lead to wide-spread increases in the plasma levels of saturated fatty acids and lipoprotein oxidation. The aim of this study is to examine whether palmitate and minimally modified low-density lipoprotein (mmLDL) exert an additive effect on macrophage activation. We found that CXCL2 and TNF-alpha secretion as well as ERK and p38 phosphorylation were additively increased by co-treatment of J774 macrophages with palmitate and mmLDL in the presence of lipopolysaccharide (LPS). Furthermore, the analysis of differentially expressed genes using the KEGG database revealed that several pathways, including cytokine-cytokine receptor interaction, and genes were significantly altered. These results were validated with real-time PCR, showing upregulation of Il-6, Csf3, Il-1beta, and Clec4d. The present study demonstrated that palmitate and mmLDL additively potentiate the LPS-induced activation of macrophages. These results suggest the existence of synergistic mechanisms by which saturated fatty acids and oxidized lipoproteins activate immune cells.
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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Microbiology (미생물학교실) > 1. Journal Papers
Yonsei Authors
Kang, Seok Min(강석민) ORCID logo https://orcid.org/0000-0001-9856-9227
Kim, Sangwoo(김상우) ORCID logo https://orcid.org/0000-0001-5356-0827
Park, Sung Ha(박성하) ORCID logo https://orcid.org/0000-0001-5362-478X
Yu, Je Wook(유제욱) ORCID logo https://orcid.org/0000-0001-5943-4071
Lee, Sang Hak(이상학) ORCID logo https://orcid.org/0000-0002-4535-3745
Hwang, Inhwa(황인화) ORCID logo https://orcid.org/0000-0001-5235-3519
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