title: Intestinal anti-inflammatory activity of luteolin: role of the aglycone in NF-κB inactivation in macrophages co-cultured with intestinal epithelial cells.
abstract: The flavonoid luteolin is reported to exert anti-inflammatory properties. In this study, we investigated whether luteolin inhibits gut inflammation, using in vivo and in vitro inflammation models. In a dextran sulfate sodium (DSS)-induced colitis mouse model, luteolin (20 and 50 mg/kg) significantly ameliorated shortening of colon length and histological score. Immunohistochemical analysis showed that luteolin also significantly inhibited infiltration of macrophages and interferon (IFN)-γ-producing CD4⁺ T cells into the colonic mucosa. Treatment with luteolin also improved IFN-γ mRNA expression in the colon. At the cellular level, a co-culture consisting of intestinal epithelial Caco-2 and macrophage RAW264.7 cells, stimulated with lipopolysaccharide, the addition of luteolin (100 μM) suppressed interleukin (IL)-8 mRNA expression in Caco-2 cells without epithelial monolayer disruption. Expression of tumor necrosis factor (TNF)-α protein and proinflammatory cytokines mRNA (TNF-α, IL-6, and IL-1β) in RAW264.7 cells were also suppressed. HPLC analysis and subsequent cellular assay revealed that aglycone of luteolin was present in the basolateral supernatant of this system at a sufficient concentration to suppress TNF-α production and nuclear factor (NF)-κB activation of RAW264.7 cells. These results suggest that the luteolin aglycones released from the Caco-2 epithelium inhibits NF-κB nuclear translocation in RAW264.7 cells, followed by reduction of TNF-α mRNA expression, which results in downregulation of IL-8 mRNA expression in Caco-2 cells. The mechanism by which aglycone inhibits inflammation is important for understanding the roles of luteolin in diet.
authors: Organization of Advanced Science and Technology, Kobe University, Rokkodai-cho 1-1, Nada-ku, Kobe 657-8501, Japan.
authors: Yosuke
authors: Y
authors: Nishitani
authors: Koji
authors: K
authors: Yamamoto
authors: Masaru
authors: M
authors: Yoshida
authors: Takeshi
authors: T
authors: Azuma
authors: Kazuki
authors: K
authors: Kanazawa
authors: Takashi
authors: T
authors: Hashimoto
authors: Masashi
authors: M
authors: Mizuno
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018938:Caco-2 Cells; D002465:Cell Movement; D002467:Cell Nucleus / Q000378:metabolism; D018920:Coculture Techniques; D003106:Colon / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D004847:Epithelial Cells; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D043183:Irritable Bowel Syndrome / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D047311:Luteolin / Q000494:pharmacology* / Q000627:therapeutic use; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism*; D021381:Protein Transport; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D016209:Interleukin-8; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D047311:Luteolin
keywords: DSS-induced colitis; TNF-α; anti-inflammatory; luteolin