Inhibitory effect of luteolin on TNF-alpha-induced IL-8 production in human colon epithelial cells.

Interleukin (IL)-8 plays a central role in the initiation and maintenance of inflammatory responses in the inflammatory bowel disease. The proinflammatory cytokine-mediated production of IL-8 requires activation of various kinases, which leads to the IkappaB degradation and NF-kappaB activation. In this study, we investigated the role of luteolin, a major flavonoid of Lonicera japonica, on TNF-alpha-induced IL-8 production in human colonic epithelial cells. HT29 cells were stimulated with TNF-alpha in the presence or absence of luteolin. IL-8 production was measured by enzyme-linked immunosorbent assay (ELISA) and reverse transcriptase-polymerase chain reaction (RT-PCR) analysis, and the mitogen-activated protein kinases (MAPKs) activation and IkappaB degradation were determined by Western blot analysis. NF-kappaB activation was assessed by the electrophoretic motility shift assay (EMSA). Luteolin suppressed TNF-alpha-induced IL-8 production in dose-dependent manner. In addition, luteolin inhibited TNF-alpha-induced phosphorylation of p38 MAPK and extracellular-regulated kinases (ERK), IkappaB degradation, and NF-kappaB activation. These results suggest that luteolin has the inhibitory effects on TNF-alpha-induced IL-8 production in the intestinal epithelial cells through blockade in the phosphorylation of MAPKs, following IkappaB degradation and NF-kappaB activation.

[1]  J. Kang,et al.  Flavones mitigate tumor necrosis factor-alpha-induced adhesion molecule upregulation in cultured human endothelial cells: role of nuclear factor-kappa B. , 2004, The Journal of nutrition.

[2]  S. Ryu,et al.  Luteolin inhibits the nuclear factor-κB transcriptional activity in Rat-1 fibroblasts , 2003 .

[3]  A. Gomez-Muñoz,et al.  Curcumin attenuates DNB-induced murine colitis. , 2003, American journal of physiology. Gastrointestinal and liver physiology.

[4]  M. Parsons,et al.  Nicotinic acetylcholine receptor subunits and receptor activity in the epithelial cell line HT29. , 2003, Life sciences.

[5]  T. K. van den Berg,et al.  Flavonoids inhibit myelin phagocytosis by macrophages; a structure-activity relationship study. , 2003, Biochemical pharmacology.

[6]  S. Deventer,et al.  From Extracellular to Intracellular Targets, Inhibiting MAP Kinases in Treatment of Crohn's Disease , 2002, Annals of the New York Academy of Sciences.

[7]  H. Ueda,et al.  Luteolin as an anti-inflammatory and anti-allergic constituent of Perilla frutescens. , 2002, Biological & pharmaceutical bulletin.

[8]  C. Roussos,et al.  Inhibition of LPS‐stimulated pathways in macrophages by the flavonoid luteolin , 2002, British journal of pharmacology.

[9]  K. Madsen,et al.  MAP kinases contribute to IL-8 secretion by intestinal epithelial cells via a posttranscriptional mechanism. , 2002, American journal of physiology. Cell physiology.

[10]  C. Szabó,et al.  Na+/H+ exchanger blockade inhibits enterocyte inflammatory response and protects against colitis. , 2002, American journal of physiology. Gastrointestinal and liver physiology.

[11]  C. Roussos,et al.  Luteolin reduces lipopolysaccharide-induced lethal toxicity and expression of proinflammatory molecules in mice. , 2002, American journal of respiratory and critical care medicine.

[12]  Philip Rosenstiel,et al.  p38 mitogen-activated protein kinase is activated and linked to TNF-alpha signaling in inflammatory bowel disease. , 2002, Journal of immunology.

[13]  R. Fando,et al.  Differential Interleukin-8 Response of Intestinal Epithelial Cell Line to Reactogenic and Nonreactogenic Candidate Vaccine Strains of Vibrio cholerae , 2001, Infection and Immunity.

[14]  C. Roussos,et al.  Luteolin inhibits an endotoxin-stimulated phosphorylation cascade and proinflammatory cytokine production in macrophages. , 2001, The Journal of pharmacology and experimental therapeutics.

[15]  C. Hagedorn,et al.  Salmonella typhimurium translocates flagellin across intestinal epithelia, inducing a proinflammatory response. , 2001, The Journal of clinical investigation.

[16]  E. Middleton,et al.  The effects of plant flavonoids on mammalian cells: implications for inflammation, heart disease, and cancer. , 2000, Pharmacological reviews.

[17]  Roger L. Williams,et al.  Structural determinants of phosphoinositide 3-kinase inhibition by wortmannin, LY294002, quercetin, myricetin, and staurosporine. , 2000, Molecular cell.

[18]  S. Mineshita,et al.  The effect of berberine chloride on experimental colitis in rats in vivo and in vitro. , 2000, The Journal of pharmacology and experimental therapeutics.

[19]  Y. B. Lee,et al.  p38 map kinase regulates TNF-alpha production in human astrocytes and microglia by multiple mechanisms. , 2000, Cytokine.

[20]  I. Serizawa,et al.  Effects of luteolin, quercetin and baicalein on immunoglobulin E‐mediated mediator release from human cultured mast cells , 2000, Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology.

[21]  N. Inagaki,et al.  Effects of Luteolin and Other Flavonoids on IgE-Mediated Allergic Reactions , 2000, Planta medica.

[22]  D. Brenner,et al.  Curcumin blocks cytokine-mediated NF-kappa B activation and proinflammatory gene expression by inhibiting inhibitory factor I-kappa B kinase activity. , 1999, Journal of immunology.

[23]  D. Brenner,et al.  TNF receptor-associated factor-2 is involved in both IL-1 beta and TNF-alpha signaling cascades leading to NF-kappa B activation and IL-8 expression in human intestinal epithelial cells. , 1999, Journal of immunology.

[24]  M. Kagnoff,et al.  Differential and regulated expression of C-X-C, C-C, and C-chemokines by human colon epithelial cells. , 1997, Gastroenterology.

[25]  J. Piette,et al.  Activation of the NF-kappaB transcription factor in a T-lymphocytic cell line by hypochlorous acid. , 1997, The Biochemical journal.

[26]  A. Baldwin,et al.  THE NF-κB AND IκB PROTEINS: New Discoveries and Insights , 1996 .

[27]  P. Gibson,et al.  Interleukin 8 secretion by colonic crypt cells in vitro: response to injury suppressed by butyrate and enhanced in inflammatory bowel disease. , 1995, Gut.

[28]  K. Mitsuyama,et al.  IL‐8 as an important chemoattractant for neutrophils in ulcerative colitis and Crohn's disease , 1994, Clinical and experimental immunology.

[29]  L. Mazzucchelli,et al.  Expression of interleukin-8 gene in inflammatory bowel disease is related to the histological grade of active inflammation. , 1994, The American journal of pathology.

[30]  A. Chen,et al.  Neutrophil-activating peptide (interleukin-8) in colonic mucosa from patients with Crohn's disease. , 1993, Scandinavian journal of gastroenterology.

[31]  C. Hawkey,et al.  Enhanced synthesis of neutrophil-activating peptide-1/interleukin-8 in active ulcerative colitis. , 1992, Clinical science.