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: Yosuke Nishitani, Koji Yamamoto, Masaru Yoshida, Takeshi Azuma, Kazuki Kanazawa, Takashi Hashimoto, Masashi Mizuno
• Journal: BioFactors (Oxford, England) (Biofactors) 2013 Sep-Oct Vol. 39 Issue 5 Pg. 522-33 ISSN: 1872-8081 [Electronic] Netherlands
• PMID: 23460110 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 International Union of Biochemistry and Molecular Biology, Inc.

Chemical References

• Anti-Inflammatory Agents
• Interleukin-8
• NF-kappa B
• Tumor Necrosis Factor-alpha
• Ptgs2 protein, mouse
• Cyclooxygenase 2
• Luteolin

Topics

• Animals
• Anti-Inflammatory Agents (pharmacology, therapeutic use)
• CD4-Positive T-Lymphocytes (immunology)
• Caco-2 Cells
• Cell Movement
• Cell Nucleus (metabolism)
• Coculture Techniques
• Colon (drug effects, immunology, pathology)
• Cyclooxygenase 2 (genetics, metabolism)
• Epithelial Cells
• Female
• Gene Expression (drug effects)
• Humans
• Interleukin-8 (genetics, metabolism)
• Irritable Bowel Syndrome (drug therapy, immunology, pathology)
• Luteolin (pharmacology, therapeutic use)
• Macrophages (drug effects, immunology, metabolism)
• Mice
• Mice, Inbred C57BL
• NF-kappa B (metabolism)
• Protein Transport
• Tumor Necrosis Factor-alpha (metabolism)