Involvement of ERK, a MAP kinase, in the production of TGF-beta by macrophages treated with liposomes composed of phosphatidylserine

Biochem Biophys Res Commun. 2004 Nov 26;324(4):1400-5. doi: 10.1016/j.bbrc.2004.09.198.


We have already reported that TGF-beta could be involved in the inhibitory effects of negatively charged liposomes composed of phosphatidylserine (PS-liposome) on the production of nitric oxide (NO) by mouse peritoneal macrophages stimulated with LPS [Biochem. Biophys. Res. Commun. 281 (2001) 614]. In this paper, we explored the mechanism by which PS-liposomes promote the production of TGF-beta and the involvement of MAP kinases. When macrophages were treated with PS-liposomes, extracellular signal-regulated kinase (ERK), a member of MAP kinase superfamily, was activated quickly and potently. However, no activation was observed with p38 MAP kinase. TGF-beta production was completely inhibited by U0126, a specific inhibitor for ERK. Furthermore, TGF-beta neutralizing antibody and U0126 decreased the inhibitory effect of PS-liposomes on NO production by macrophages. These findings suggested that TGF-beta is the factor produced by PS-liposomes that suppresses production of NO, and the ERK signaling pathway is intimately involved in TGF-beta production by macrophages following treatment with PS-liposomes.

MeSH terms

  • Animals
  • Extracellular Signal-Regulated MAP Kinases / physiology*
  • Liposomes / chemistry
  • Liposomes / pharmacology*
  • Macrophages / drug effects
  • Macrophages / enzymology
  • Macrophages / metabolism*
  • Male
  • Mice
  • Nitric Oxide / biosynthesis
  • Phosphatidylserines / pharmacology*
  • Transforming Growth Factor beta / biosynthesis*


  • Liposomes
  • Phosphatidylserines
  • Transforming Growth Factor beta
  • Nitric Oxide
  • Extracellular Signal-Regulated MAP Kinases