Sphingosylphosphorylcholine and lysosulfatide have inverse regulatory functions in monocytic cell differentiation into macrophages

Hiroshi Yamamoto, Yuko Naito, Maho Okano, Takayuki Kanazawa, Hiromu Takematsu, Yasunori Kozutsumi

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)

Abstract

Sphingolipids act as signaling mediators that regulate a diverse range of cellular events. Although numerous sphingolipid functions have been studied, little is known about the effect of sphingolipids on monocyte differentiation into macrophages. Here, we report that two lysosphingolipids, sphingosylphosphorylcholine (SPC) and lysosulfatide (LSF), inversely affect macrophagic differentiation of monocytic cell lines, U937 and THP-1. Molecular analyses revealed that SPC enhances, whereas LSF suppresses, phorbol ester-induced classical (M1-polarized) differentiation to macrophages. The expression of CD11b, a macrophage marker, was induced in accordance with the activation status of the Raf/MEK/ERK signaling pathway in which SPC and LSF had opposite effects. Pharmacological inhibition of this pathway aborted the differentiation, indicating that this signaling pathway is required. Consistently, SPC promoted, while LSF inhibited, monocyte adhesion to fibronectin, through the phosphatidylinositol-3-kinase (PI3K)/Akt signaling pathway. The effects of SPC on Raf/MEK/ERK and PI3K/Akt signaling were dependent on Gi/o, whereas the SPC-induced calcium influx was dependent on Gq. Thus SPC utilizes G-protein coupled receptor. In contrast, the effects of LSF were independent of Gi/o and Gq. These results suggest that SPC enhances, whereas LSF suppresses, monocyte differentiation into macrophages through regulating the Raf/MEK/ERK and PI3K/Akt signaling pathways via distinct mechanisms.

Original languageEnglish
Pages (from-to)83-91
Number of pages9
JournalArchives of Biochemistry and Biophysics
Volume506
Issue number1
DOIs
Publication statusPublished - 01-02-2011
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology

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