Modulation of nitric oxide production in RAW 264.7 cells by transforming growth factor-beta and interleukin-10: differential effects on free and encapsulated immunomodulator.
The mouse macrophage cell line RAW 264.7 can be stimulated to produce nitric oxide (NO) by muramyltripeptide cholesterol included within biodegradable poly(D,L-lactide) nanocapsules (NC MTPChol). The aim of this work was to determine whether one or both of the cytokines transforming growth factor-beta (TGF-beta) and interleukin-10 (IL-10) could be responsible for feedback control seen at high concentrations. Activated RAW 264.7 cells produced TGFbeta1. When exogenous TGF-beta1 was added during stimulation, a dose-dependent inhibition of NO production was observed when NC MTP-Chol was used, whereas activation by the soluble muramyl dipeptide (MDP) was not affected. Furthermore, addition of a blocking antibody to TGF-beta arrested the fall in NO production seen at high concentrations of NC MTP-Chol. Addition of IL-10 during RAW 264.7 cell activation also reduced NO production; however, in this case, both NC MTP-Chol and MDP were equally affected. The presence of anti-IL-10 antibody during activation significantly increased NO production.
Seyler
I
I
URA CNRS 1218, Centre d'Etudes Pharmaceutiques, Université, Paris-Sud, Châtenay-Malabry, France.
Appel
M
M
Devissaguet
J P
JP
Legrand
P
P
Barratt
G
G
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology; D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D002460:Cell Line; D002788:Cholesterol Esters / Q000494:pharmacology; D004790:Enzyme Induction / Q000187:drug effects; D016753:Interleukin-10 / Q000494:pharmacology*; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D010587:Phagocytosis / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D000276:Adjuvants, Immunologic; D002788:Cholesterol Esters; D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D009569:Nitric Oxide; D000119:Acetylmuramyl-Alanyl-Isoglutamine; C047489:N-acetylmuramyl-alanyl-isoglutamine-alanyl-cholesterol; D019001:Nitric Oxide Synthase