RESUMO
Active Hexose Correlated Compound (AHCC) is an immunostimulatory nutritional supplement. AHCC effects and mechanism of action on intestinal epithelial cells or monocytes are poorly described. AHCC was added to the culture medium of intestinal epithelial cells (IEC18 and HT29 cells) and monocytes (THP-1 cells) and assessed the secretion of proinflammatory cytokines by ELISA. Inhibitors of NFκB and MAPKs were used to study signal transduction pathways while TLR4 and MyD88 were silenced in IEC18 cells using shRNA. It was found that AHCC induced GROα and MCP1 secretion in IEC18 and IL-8 in HT29 cells. These effects depended on NFκB activation, and partly on MAPKs activation and on the presence of MyD88 and TLR4. In THP-1 cells AHCC evoked IL-8, IL-1ß and TNF-α secretion. The induction of IL-8 depended on JNK and NFκB activation. Therefore, AHCC exerts immunostimulatory effects on intestinal epithelial cells and monocytes involving TLR4/MyD88 and NFκB/MAPK signal transduction pathways.
Assuntos
Células Epiteliais/efeitos dos fármacos , Fatores Imunológicos/farmacologia , Macrófagos/efeitos dos fármacos , Proteínas Quinases Ativadas por Mitógeno/imunologia , Fator 88 de Diferenciação Mieloide/imunologia , NF-kappa B/imunologia , Polissacarídeos/farmacologia , Receptor 4 Toll-Like/imunologia , Animais , Linhagem Celular , Suplementos Nutricionais/análise , Células Epiteliais/imunologia , Humanos , Fatores Imunológicos/imunologia , Intestinos/citologia , Intestinos/efeitos dos fármacos , Intestinos/imunologia , Macrófagos/imunologia , Proteínas Quinases Ativadas por Mitógeno/genética , Fator 88 de Diferenciação Mieloide/genética , NF-kappa B/genética , Polissacarídeos/imunologia , Ratos , Receptor 4 Toll-Like/genéticaAssuntos
Acenocumarol/efeitos adversos , Anticoagulantes/efeitos adversos , Antifúngicos/efeitos adversos , Morfolinas/efeitos adversos , Idoso , Valva Aórtica , Interações Medicamentosas , Feminino , Próteses Valvulares Cardíacas , Humanos , Coeficiente Internacional Normatizado , Pessoa de Meia-Idade , Onicomicose/tratamento farmacológicoRESUMO
Active hexose correlated compound (AHCC) is a product prepared from the mycelium of edible Basidiomycete fungi that contains oligosaccharides. Here we have studied the antiinflammatory effect of AHCC in the trinitrobenzenesulfonic acid (TNBS) model of colitis in rats. Rats received AHCC (100 or 500 mg/kg) daily starting 2 d before (pretreatment) colitis induction and were killed 6 d after the TNBS challenge. The status of the rats was assessed by morphological and biochemical methods. The effect of AHCC on the colonic microflora was also assessed by studying the bacteria profile in feces by standard culture techniques. AHCC administration attenuated colonic inflammation, improving rat weight, food intake, damage score, extension of necrosis, colonic weight, colonic weight-to-length ratio, myeloperoxidase and alkaline phosphatase activities, glutathione concentration, and the expression of proinflammatory cytokines and chemokines (IL-1beta, IL-1 receptor antagonist, TNF, and monocyte chemoattractant protein-1) and of mucins 2-4 and trefoil factor 3. The magnitude of the antiinflammatory effect of AHCC was similar to that of sulfasalazine (200 mg/kg). The study of colonic microflora indicated that rats treated with AHCC had higher aerobic and lactic acid bacteria counts as well as higher bifidobacteria counts, whereas clostridia were reduced when compared with the TNBS group. Therefore, our results indicate that AHCC is antiinflammatory and could be useful as a prebiotic to design functional foods for inflammatory bowel disease patients.
