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

doi:10.1371/journal.pone.0193649

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

Department of Internal Medicine

Research output: Contribution to journal › Article › peer-review

9 Citations (Scopus)

Abstract

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-α secretion as well as ERK and p38 phosphorylation were additively increased by cotreatment 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-1β, 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.

Original language	English
Article number	e0193649
Journal	PloS one
Volume	13
Issue number	3
DOIs	https://doi.org/10.1371/journal.pone.0193649
Publication status	Published - 2018 Mar

Bibliographical note

Funding Information:
This research was financially supported by a faculty research grant from Yonsei University College of Medicine for 2011 (6-2011-0162) (SH Lee), the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science, and Technology (2012R1A4A1029061 and 2014R1A1A2056104) (SH Lee), the Bio & Medical Technology Development Program of the NRF funded by the Korean government, MSIP (2015M3A9B6029138) (SH Lee), the National Research Council of Science & Technology (NST) grant by the Korean government (MSIP) (No. CAP-12-2- KBSI) (SH Lee), a faculty research grant of Yonsei University College of Medicine (6-2016-0081) (S Kim), and a grant HL135737 from the US National Institute of Health (Y.I.Miller). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Publisher Copyright:
© 2018 Ann et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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title = "Palmitate and minimally-modified low-density lipoprotein cooperatively promote inflammatory responses in macrophages",

abstract = "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-α secretion as well as ERK and p38 phosphorylation were additively increased by cotreatment 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-1β, 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.",

author = "Ann, {Soo Jin} and Kim, {Ka Kyung} and Cheon, {Eun Jeong} and Noh, {Hye Min} and Inhwa Hwang and Yu, {Je Wook} and Sungha Park and Kang, {Seok Min} and Ichiro Manabe and Miller, {Yury I.} and Sangwoo Kim and Lee, {Sang Hak}",

note = "Funding Information: This research was financially supported by a faculty research grant from Yonsei University College of Medicine for 2011 (6-2011-0162) (SH Lee), the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science, and Technology (2012R1A4A1029061 and 2014R1A1A2056104) (SH Lee), the Bio & Medical Technology Development Program of the NRF funded by the Korean government, MSIP (2015M3A9B6029138) (SH Lee), the National Research Council of Science & Technology (NST) grant by the Korean government (MSIP) (No. CAP-12-2- KBSI) (SH Lee), a faculty research grant of Yonsei University College of Medicine (6-2016-0081) (S Kim), and a grant HL135737 from the US National Institute of Health (Y.I.Miller). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Publisher Copyright: {\textcopyright} 2018 Ann et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.",

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AU - Kim, Ka Kyung

AU - Cheon, Eun Jeong

AU - Noh, Hye Min

AU - Hwang, Inhwa

AU - Yu, Je Wook

AU - Park, Sungha

AU - Kang, Seok Min

AU - Manabe, Ichiro

AU - Miller, Yury I.

AU - Kim, Sangwoo

AU - Lee, Sang Hak

N1 - Funding Information: This research was financially supported by a faculty research grant from Yonsei University College of Medicine for 2011 (6-2011-0162) (SH Lee), the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science, and Technology (2012R1A4A1029061 and 2014R1A1A2056104) (SH Lee), the Bio & Medical Technology Development Program of the NRF funded by the Korean government, MSIP (2015M3A9B6029138) (SH Lee), the National Research Council of Science & Technology (NST) grant by the Korean government (MSIP) (No. CAP-12-2- KBSI) (SH Lee), a faculty research grant of Yonsei University College of Medicine (6-2016-0081) (S Kim), and a grant HL135737 from the US National Institute of Health (Y.I.Miller). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Publisher Copyright: © 2018 Ann et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

PY - 2018/3

Y1 - 2018/3

N2 - 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-α secretion as well as ERK and p38 phosphorylation were additively increased by cotreatment 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-1β, 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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Palmitate and minimally-modified low-density lipoprotein cooperatively promote inflammatory responses in macrophages

Abstract

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