Involvement of TGF-beta in inhibitory effects of negatively charged liposomes on nitric oxide production by macrophages stimulated with LPS

We examined the role of TGF-beta in the inhibitory effects of negatively ch arged liposomes composed of phosphatidylserine (PS-liposomes) on nitric oxi de (NO) production by macrophages stimulated with LPS. The expression of TG F-beta mRNA increased when mouse peritoneal macrophages were treated with P S-liposomes. The inhibitory effect of PS-liposomes on NO production was res tored by treatment with anti-TGF-beta antibody. Furthermore, NO production, iNOS mRNA expression, and iNOS protein induction by LPS were inhibited by treatment of macrophages with TGF-beta as well as PS-liposomes. These resul ts indicated that PS-liposomes down-regulate NO production by macrophages t hrough the induction of TGF-beta and suggested that TGF-beta may suppress N O production upstream of the transcription of iNOS mRNA. (C) 2001 Academic Press.