title: Involvement of ERK, a MAP kinase, in the production of TGF-beta by macrophages treated with liposomes composed of phosphatidylserine.
abstract: 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.
authors.affiliation: School of Pharmacy, Tokyo University of Pharmacy and Life Science, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Otsuka
authors.forename: Seishi
authors.initials: S
authors.lastname: Tsuchiya
authors.forename: Yukihiko
authors.initials: Y
authors.lastname: Aramaki
mesh_terms: D000818:Animals; D048049:Extracellular Signal-Regulated MAP Kinases / Q000502:physiology*; D008081:Liposomes / Q000737:chemistry / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D051379:Mice; D009569:Nitric Oxide / Q000096:biosynthesis; D010718:Phosphatidylserines / Q000494:pharmacology*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis*
chemical_list: D008081:Liposomes; D010718:Phosphatidylserines; D016212:Transforming Growth Factor beta; D009569:Nitric Oxide; D048049:Extracellular Signal-Regulated MAP Kinases