title: Essential Role of Lysophosphatidylcholine Acyltransferase 3 in the Induction of Macrophage Polarization in PMA-Treated U937 Cells.
abstract: Lysophospholipid acyltransferases (LPLATs) regulate the diversification of fatty acid composition in biological membranes. Lysophosphatidylcholine acyltransferases (LPCATs) are members of the LPLATs that play a role in inflammatory responses. M1 macrophages differentiate in response to lipopolysaccharide (LPS) and are pro-inflammatory, whereas M2 macrophages, which differentiate in response to interleukin-4 (IL-4), are anti-inflammatory and involved in homeostasis and wound healing. In the present study, we showed that LPCATs play an important role in M1/M2-macrophage polarization. LPS changed the shape of PMA-treated U937 cells from rounded to spindle shaped and upregulated the mRNA and protein expression of the M1 macrophage markers CXCL10, TNF-α, and IL-1β. IL-4 had no effect on the shape of PMA-treated U937 cells and upregulated the M2 macrophage markers CD206, IL-1ra, and TGF-β in PMA-treated U937 cells. These results suggest that LPS and IL-4 promote the differentiation of PMA-treated U937 cells into M1- and M2-polarized macrophages, respectively. LPS significantly downregulated the mRNA expression of LPCAT3, one of four LPCAT isoforms, and suppressed its enzymatic activity toward linoleoyl-CoA and arachidonoyl-CoA in PMA-treated U937 cells. LPCAT3 knockdown induced a spindle-shaped morphology typical of M1-polarized macrophages, and increased the secretion of CXCL10 and decreased the levels of CD206 in IL-4-activated U937 cells. This indicates that knockdown of LPCAT3 shifts the differentiation of PMA-treated U937 cells to M1-polarized macrophages. Our findings suggest that LPCAT3 plays an important role in M1/M2-macrophage polarization, providing novel potential therapeutic targets for the regulation of immune and inflammatory disorders.
authors.affiliation: Division of Infections and Molecular Biology, Department of Health Promotion, Kyushu Dental University, Kitakyushu, Fukuoka, 803-8580, Japan.|Division of Oral and Maxillofacial Surgery, Department of Science of Physical Function, Kyushu Dental University, Kitakyushu, Fukuoka, 803-8580, Japan.
authors.forename: Kosuke
authors.initials: K
authors.lastname: Taniguchi
authors.affiliation: Department of Oral Functional Management, Kyushu Dental University, Kitakyushu, Fukuoka, 803-8580, Japan.
authors.forename: Hisako
authors.initials: H
authors.lastname: Hikiji
authors.affiliation: Division of Infections and Molecular Biology, Department of Health Promotion, Kyushu Dental University, Kitakyushu, Fukuoka, 803-8580, Japan.
authors.forename: Toshinori
authors.initials: T
authors.lastname: Okinaga
authors.affiliation: Department of Lipid Signaling, Research Institute, National Center for Global Health and Medicine, Tokyo, 162-8655, Japan.
authors.forename: Tomomi
authors.initials: T
authors.lastname: Hashidate-Yoshida
authors.affiliation: Department of Lipid Signaling, Research Institute, National Center for Global Health and Medicine, Tokyo, 162-8655, Japan.|CREST, Japan Science and Technology Agency, Kawaguchi, Saitama, 332-0012, Japan.
authors.forename: Hideo
authors.initials: H
authors.lastname: Shindou
authors.affiliation: Division of Infections and Molecular Biology, Department of Health Promotion, Kyushu Dental University, Kitakyushu, Fukuoka, 803-8580, Japan.
authors.forename: Wataru
authors.initials: W
authors.lastname: Ariyoshi
authors.affiliation: Department of Lipid Signaling, Research Institute, National Center for Global Health and Medicine, Tokyo, 162-8655, Japan.|Department of Biochemistry and Molecular Biology (Lipidomics), Faculty of Medicine, University of Tokyo, 113-0033, Japan.
authors.forename: Takao
authors.initials: T
authors.lastname: Shimizu
authors.affiliation: Division of Oral and Maxillofacial Surgery, Department of Science of Physical Function, Kyushu Dental University, Kitakyushu, Fukuoka, 803-8580, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Tominaga
authors.affiliation: Division of Infections and Molecular Biology, Department of Health Promotion, Kyushu Dental University, Kitakyushu, Fukuoka, 803-8580, Japan.
authors.forename: Tatsuji
authors.initials: T
authors.lastname: Nishihara
mesh_terms: D008243:1-Acylglycerophosphocholine O-Acyltransferase / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects; D016764:Cell Polarity / Q000187:drug effects / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D006801:Humans; D007249:Inflammation / Q000235:genetics* / Q000473:pathology; D015847:Interleukin-4 / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D010767:Phosphorylcholine / Q000031:analogs & derivatives / Q000494:pharmacology; D011109:Polymethacrylic Acids / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D020298:U937 Cells
chemical_list: D008070:Lipopolysaccharides; D011109:Polymethacrylic Acids; D012333:RNA, Messenger; C500651:poly(MPC-co-MA); D010767:Phosphorylcholine; D015847:Interleukin-4; D008243:1-Acylglycerophosphocholine O-Acyltransferase; C543069:LPCAT3 protein, human
keywords: LYSOPHOSPHATIDYLCHOLINE ACYLTRANSFERASE 3; MACROPHAGE POLARIZATION; U937 CELLS