Autor |
Procópio, Daniela O.
![]() ![]() Teixeira, Mauro M. ![]() Camargo, Maristela M. ![]() Travassos, Luiz R. ![]() Ferguson, Michael AJ ![]() Almeida, Igor C. ![]() Gazzinelli, Ricardo T. ![]() |
Instituição | Universidade Federal de Minas Gerais (UFMG) FIOCRUZ Universidade Federal de São Paulo (UNIFESP) Univ Dundee |
Resumo | 1 Microbial stimuli such as bacterial lipopolysaccharide (LPS) or glycosylphosphatidylinositol-mucins derived from Trypanosoma cruzi trypomastigotes (tGPI-mucins) are effective stimulators of the synthesis of cytokines by macrophages. Here, we evaluated the ability of cyclic AMP mimetic or elevating agents to modulate TNF-alpha and IL-12 synthesis by murine inflammatory macrophages.2 Cholera Toxin (ChTx) inhibited tGPI-mucins (2.5 nM) or LPS (100 ng ml(-1)) induced TNF-alpha and IL-12(p40) synthesis in a concentration-dependent manner. Similarly, the cyclic AMP mimetics, 8-bromo cyclic AMP or dibutyryl cyclic AMP, or prostaglandin (PG) E-2 inhibited the synthesis of both cytokines by macrophages exposed to microbial stimuli.3 the protein kinase A inhibitor H-89 partially reversed the inhibitory effects of dibutyryl cyclic AMP and PGE(2) on both IL-12(p40) and TNF-alpha synthesis.4 Pretreatment of macrophages with dibutyryl cyclic AMP or ChTx augmented the synthesis of IL-10 triggered by microbial products. Elevation of cyclic AMP inhibited the synthesis of TNF-alpha, but not IL-12(p40), by inflammatory macrophages from IL-10 knockout mice.5 Kinetic studies showed that synthesis of both TNF-alpha and IL-10 peaked at 8 h and IL-12 at 24 h after stimulation with microbial stimuli.6 Together, our findings favour the hypothesis that the cyclic AMP inhibitory activity on IL-12(p40) but not on TNF-alpha synthesis is dependent on de novo protein synthesis, most likely involving IL-10, by macrophages stimulated with microbial products. Accordingly, dibutyryl cyclic AMP inhibited IL-12(p40) synthesis only when added before or at the same time of the stimuli. in contrast, the effect of this cyclic AMP analogue on TNF-alpha synthesis was protracted and observed even 2 h after the addition of the stimuli. |
Assunto |
cyclic AMP
glycosylphosphatidylinositol-mucins IL-12 IL-10 lipopolysaccharide macrophage microbial stimuli prostaglandins TNF-alpha Trypanosoma cruzi |
Idioma | Inglês |
Data | 1999-07-01 |
Publicado em | British Journal of Pharmacology. Basingstoke: Stockton Press, v. 127, n. 5, p. 1195-1205, 1999. |
ISSN | 0007-1188 (Sherpa/Romeo, fator de impacto) |
Editor | Stockton Press |
Extensão | 1195-1205 |
Fonte |
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Direito de acesso | Acesso aberto ![]() |
Tipo | Artigo |
Web of Science | WOS:000081391700019 |
URI | http://repositorio.unifesp.br/handle/11600/26096 |
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