title: Olive oil phenolic extract regulates interleukin-8 expression by transcriptional and posttranscriptional mechanisms in Caco-2 cells.
abstract: In this study, we investigated the ability of a phenolic extract from extra virgin olive oil (OPE) to modulate the inflammatory response in intestinal epithelial cells. Undifferentiated and differentiated Caco-2 cells were challenged with LPS (50 μg/mL) or IL-1β (5 ng/mL) to mimic the early and intermediate phase of intestinal inflammation, respectively. The effects of OPE on nuclear factor-κB-driven transcription and IL-8 promoter activity were evaluated in transfection assays, coupled to p65 nuclear translocation. Modulation of IL-8 mRNA levels by OPE was measured by quantitative RT-PCR while effects on protein levels by ELISA. Specific mitogen activated protein kinases inhibitors were used to investigate mRNA stability and the involvement of related signaling pathways. OPE prevented IL-8 expression and secretion in LPS-treated Caco-2 cells. In the presence of IL-1β OPE exhibited opposing effects on IL-8 gene transcription and mRNA/protein levels. While in IL-1β-treated cells IL-8 promoter activity was inhibited by treatment with OPE, IL-8 mRNA stability was strongly enhanced, leading to increased protein expression. Inhibitors of p38 and extracellular signal-regulated kinases partly prevented OPE effect on IL-8 mRNA levels. Intestinal epithelial cells represent a direct target of the action of olive oil phenols where they regulate IL-8 expression by transcriptional and posttranscriptional mechanisms.
authors.affiliation: Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milan, Italy.
authors.forename: Eri
authors.initials: E
authors.lastname: Muto
authors.affiliation: Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milan, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Dell'Agli
authors.affiliation: Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milan, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Sangiovanni
authors.affiliation: Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milan, Italy.
authors.forename: Nico
authors.initials: N
authors.lastname: Mitro
authors.affiliation: Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milan, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Fumagalli
authors.affiliation: Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milan, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Crestani
authors.affiliation: Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milan, Italy.
authors.forename: Emma
authors.initials: E
authors.lastname: De Fabiani
authors.affiliation: Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milan, Italy.
authors.forename: Donatella
authors.initials: D
authors.lastname: Caruso
mesh_terms: D018938:Caco-2 Cells; D002454:Cell Differentiation / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000009:adverse effects; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D000069463:Olive Oil / Q000494:pharmacology*; D010636:Phenols / Q000494:pharmacology*; D010936:Plant Extracts / Q000494:pharmacology*; D011401:Promoter Regions, Genetic; D020871:RNA Stability; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D015533:Transcriptional Activation
chemical_list: C508606:CXCL8 protein, human; D053583:Interleukin-1beta; D016209:Interleukin-8; D008070:Lipopolysaccharides; D016328:NF-kappa B; D000069463:Olive Oil; D010636:Phenols; D010936:Plant Extracts; D012333:RNA, Messenger; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: Extra-virgin olive oil; IL-8; Inflammation; Intestine; Phenols