title: The nutritional supplement Active Hexose Correlated Compound (AHCC) has direct immunomodulatory actions on intestinal epithelial cells and macrophages involving TLR/MyD88 and NF-κB/MAPK activation.
abstract: 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-1β 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.
authors.affiliation: Department of Environmental Protection, Consejo Superior de Investigaciones Científicas, C/ Profesor Albareda 1, E-18008 Granada, Spain.
authors.forename: Abdelali
authors.initials: A
authors.lastname: Daddaoua
authors.forename: Enrique
authors.initials: E
authors.lastname: Martínez-Plata
authors.forename: Mercedes
authors.initials: M
authors.lastname: Ortega-González
authors.forename: Borja
authors.initials: B
authors.lastname: Ocón
authors.forename: Carlos J
authors.initials: CJ
authors.lastname: Aranda
authors.forename: Antonio
authors.initials: A
authors.lastname: Zarzuelo
authors.forename: María D
authors.initials: MD
authors.lastname: Suárez
authors.forename: Fermín Sánchez
authors.initials: FS
authors.lastname: de Medina
authors.forename: Olga
authors.initials: O
authors.lastname: Martínez-Augustin
mesh_terms: D000818:Animals; D002460:Cell Line; D019587:Dietary Supplements / Q000032:analysis; D004847:Epithelial Cells / Q000187:drug effects* / Q000276:immunology; D006801:Humans; D007155:Immunologic Factors / Q000276:immunology / Q000494:pharmacology*; D007422:Intestines / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000276:immunology*; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000276:immunology*; D016328:NF-kappa B / Q000235:genetics / Q000276:immunology*; D011134:Polysaccharides / Q000276:immunology / Q000494:pharmacology*; D051381:Rats; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000276:immunology*
chemical_list: D007155:Immunologic Factors; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; D011134:Polysaccharides; D051197:Toll-Like Receptor 4; D020928:Mitogen-Activated Protein Kinases; C499366:Active Hexose Correlated Compound