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1.
J Leukoc Biol ; 62(3): 374-80, 1997 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-9307077

RESUMO

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.


Assuntos
Adjuvantes Imunológicos/farmacologia , Interleucina-10/farmacologia , Macrófagos/efeitos dos fármacos , Óxido Nítrico/biossíntese , Fator de Crescimento Transformador beta/farmacologia , Acetilmuramil-Alanil-Isoglutamina/análogos & derivados , Acetilmuramil-Alanil-Isoglutamina/química , Acetilmuramil-Alanil-Isoglutamina/farmacologia , Animais , Linhagem Celular , Ésteres do Colesterol/farmacologia , Indução Enzimática/efeitos dos fármacos , Ativação de Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Óxido Nítrico Sintase/metabolismo , Fagocitose/efeitos dos fármacos
2.
Int J Immunopharmacol ; 18(6-7): 385-92, 1996.
Artigo em Inglês | MEDLINE | ID: mdl-9024940

RESUMO

The present study evaluates the ability of a new drug carrier: nanocapsules of poly(D,L-lactide) containing muramyldipeptide-L-alanyl-cholesterol (MTP-Chol NC) to induce activation of mouse macrophage cell lines. MTP-Chol NC stimulated nitric oxide (NO) expression and tumor necrosis factor-alpha (TNF-alpha) production, these are two important mediators of macrophage-mediated cytotoxicity. The encapsulated form was more effective than free muramyldipeptide, at low immunomodulator concentrations. The dose-response curves were completely different for NO and TNF-alpha, implying different regulatory mechanisms. In RAW 264.7 cells, the addition of anti-TNF-alpha antibodies during the activation period did not affect the level of nitrite induced by MTP-Chol Nc and lipopolysaccharide. Therefore, autocrine stimulation by TNF-alpha did not contribute to NO production. On the other hand, the presence of an NO synthase inhibitor led to an increase in TNF-alpha secretion. In J774.A1 cells, which were activated by MTP-Chol NC and interferon-gamma, TNF-alpha production seemed to act as a second messenger. Thus, under certain conditions, NO can play a role in modulating the cytotoxic activities of mouse macrophages.


Assuntos
Adjuvantes Imunológicos/farmacologia , Glicopeptídeos/farmacologia , Macrófagos/metabolismo , Ácidos Murâmicos/farmacologia , Óxido Nítrico Sintase/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Animais , Cápsulas , Células Cultivadas , L-Lactato Desidrogenase/metabolismo , Lipopolissacarídeos/farmacologia , Ativação de Macrófagos/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Macrófagos/enzimologia , Camundongos , Nitritos/metabolismo
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