title: A citrus extract containing flavanones represses plasminogen activator inhibitor-1 (PAI-1) expression and regulates multiple inflammatory, tissue repair, and fibrosis genes in human colon fibroblasts.
abstract: The consumption of flavonoid-rich Citrus extracts has been associated with multiple beneficial effects including anti-inflammatory properties, but the potential effects on the inflammatory responses in the gut have not been thoroughly investigated. We used microarrays to search for molecular changes induced in human colon fibroblasts in response to the exposure to a flavanone-rich bitter orange extract under physiologically representative conditions. Dietary nontoxic levels of the predigested extract induced moderate but significant changes in the expression of genes associated with tissue repair and inflammation. Among the top regulated genes, plasminogen activator inhibitor 1 (PAI-1) was downregulated, and the matrix metallopeptidase 12 (MMP-12) was upregulated (mRNA and protein levels). Both proteins are involved in extracellular matrix (ECM) remodeling and fibroblast migration. The extract also affected the fibroblast migration and reduced monocyte adhesion, but the response was different in unstimulated cells and in cells pretreated with TNF-alpha. Collectively, these results were indicative of a moderate activation of the colon fibroblast inflammation-related function after exposure to the extract. Further investigations are required to identify the in vivo role of this Citrus derived extract in the maintenance of the normal balance in the intestine and in the pathogenesis of inflammatory diseases.
authors.affiliation: Centro de Edafología y Biología Aplicada del Segura-Consejo Superior de Investigaciones Científicas (CEBAS-CSIC), Murcia, Spain.
authors.forename: Juan A
authors.initials: JA
authors.lastname: Giménez-Bastida
authors.forename: Mario
authors.initials: M
authors.lastname: Martínez-Florensa
authors.forename: Juan-Carlos
authors.initials: JC
authors.lastname: Espín
authors.forename: Francisco A
authors.initials: FA
authors.lastname: Tomás-Barberán
authors.forename: María-Teresa
authors.initials: MT
authors.lastname: García-Conesa
mesh_terms: D000893:Anti-Inflammatory Agents; D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D002957:Citrus / Q000737:chemistry*; D003106:Colon / Q000737:chemistry*; D004063:Digestion; D005347:Fibroblasts / Q000737:chemistry; D005355:Fibrosis / Q000235:genetics; D044950:Flavanones / Q000032:analysis* / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D053508:Matrix Metalloproteinase 12 / Q000032:analysis / Q000235:genetics; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D017395:Plasminogen Activator Inhibitor 1 / Q000032:analysis / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D000893:Anti-Inflammatory Agents; D044950:Flavanones; D010936:Plant Extracts; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D053508:Matrix Metalloproteinase 12