RRC ID 65552
Author Taniguchi K, Hikiji H, Okinaga T, Hashidate-Yoshida T, Shindou H, Ariyoshi W, Shimizu T, Tominaga K, Nishihara T.
Title Essential Role of Lysophosphatidylcholine Acyltransferase 3 in the Induction of Macrophage Polarization in PMA-Treated U937 Cells.
Journal J Cell Biochem
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.
Volume 116(12)
Pages 2840-8
Published 2015-12-1
DOI 10.1002/jcb.25230
PMID 25994902
MeSH 1-Acylglycerophosphocholine O-Acyltransferase / genetics 1-Acylglycerophosphocholine O-Acyltransferase / metabolism* Cell Differentiation / drug effects Cell Polarity / drug effects Cell Polarity / genetics* Gene Expression Regulation, Developmental / drug effects Humans Inflammation / genetics* Inflammation / pathology Interleukin-4 / biosynthesis Lipopolysaccharides / pharmacology Macrophages / drug effects Macrophages / metabolism* Phosphorylcholine / analogs & derivatives Phosphorylcholine / pharmacology Polymethacrylic Acids / pharmacology RNA, Messenger / biosynthesis U937 Cells
IF 4.237
Human and Animal Cells U-937 DE-4(RCB0435)