title: Regulation of macrophage differentiation and polarization by group IVC phospholipase A₂.
abstract: Although the cellular function of group IVC phospholipase A(2) (IVC-PLA(2)) remains to be understood, the expression of IVC-PLA(2) in human monocytic THP-1 cells was increased during phorbol ester-induced macrophage differentiation. We therefore examined the role of IVC-PLA(2) in macrophage differentiation using THP-1 cells. Two THP-1 cell lines stably expressing IVC-PLA(2)-specific shRNA were established. Differentiation and maturation into macrophages on treatment with phorbol ester were facilitated by knockdown of IVC-PLA(2) without the compensatory induction of mRNA expression for other group IV and VI PLA(2)s. Furthermore, the enhancement of macrophage differentiation by IVC-PLA(2)-knockdown were abolished by treatment with lysophosphatidylcholine, a metabolite of phospholipids generated by PLA(2)-mediated hydrolysis, indicating that PLA(2) activity is necessary for the inhibition of macrophage differentiation by IVC-PLA(2). Additionally, we found that the differentiation into classically activated M1 macrophage was superior in IVC-PLA(2)-knockdown cells, whereas the differentiation into alternatively activated M2 macrophage was suppressed by IVC-PLA(2)-knockdown. These findings suggest that IVC-PLA(2) is involved in regulations of macrophage differentiation and macrophage polarization.
authors: Department of Pathological Biochemistry, Kyoto Pharmaceutical University, Kyoto 607-8414, Japan.
authors: Keiichi
authors: K
authors: Ishihara
authors: Asuka
authors: A
authors: Kuroda
authors: Kanako
authors: K
authors: Sugihara
authors: Shiho
authors: S
authors: Kanai
authors: Takeshi
authors: T
authors: Nabe
authors: Satoshi
authors: S
authors: Akiba
mesh_terms: D002448:Cell Adhesion; D002454:Cell Differentiation; D016764:Cell Polarity; D002478:Cells, Cultured; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D055785:Gene Knockdown Techniques; D054513:Group IV Phospholipases A2 / Q000235:genetics / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells / Q000502:physiology; D006801:Humans; D008244:Lysophosphatidylcholines / Q000378:metabolism; D008264:Macrophages / Q000201:enzymology / Q000502:physiology*; D009000:Monocytes / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics
chemical_list: D005230:Fatty Acids, Nonesterified; D008244:Lysophosphatidylcholines; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D054513:Group IV Phospholipases A2