Lipoxin A4 reduces lipopolysaccharide-induced inflammation in macrophages and intestinal epithelial cells through inhibition of nuclear factor-κB activation

Izumi Kure, Shin Nishiumi, Yosuke Nishitani, Takeshi Tanoue, Tsukasa Ishida, Masashi Mizuno, Tsuyoshi Fujita, Hiromu Kutsumi, Makoto Arita, Takeshi Azuma, Masaru Yoshida

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

Lipoxins, which are bioactive lipids derived from ω-6 polyunsaturated fatty acids, play important roles in various biological functions. In this study, the anti-inflammatory effects of lipoxin A4 (LXA4; 5S,6R,15Strihydroxy-7,9,13-trans-11-eicosatetraenoic acid) were investigated in in vitro cultured cell experiments and in vivo animal experiments. In mouse peritoneal macrophages and mouse macrophage cell line RAW264.7 cells, LXA4 reduced the lipopolysaccharide (LPS)-induced increase in the mRNA expression level of tumor necrosis factor (TNF)-α. LXA4 also reduced the LPS-induced nuclear translocation of nuclear factor-κB (NF-κB). In an LPS-induced acute inflammation mouse model, the injection of LXA4 at 5 μg/kg b.wt. led to down-regulation of the TNF-α level in serum and the TNF-α mRNA expression level in intestinal epithelial cells. Moreover, LXA4 reduced the LPS-caused phosphorylation of IκB kinases, IκB, and NF-κB, the degradation of IκB, and the nuclear translocation of NF-κB in intestinal epithelial cells. In a coculture system using RAW264.7 cells and human colon carcinoma cell line Caco-2 cells, treatment with LXA4 to Caco-2 cells led to reduction of LPS-evoked TNF-α production in RAW264.7 cells and interleukin-8 mRNA expression in Caco-2 cells. These results indicate that LXA4 exerts anti-inflammatory effects through inhibition of NF-κB activation, and, therefore, LXA4 may be useful as a therapeutic strategy against intestinal mucosa inflammation.

Original languageEnglish
Pages (from-to)541-548
Number of pages8
JournalJournal of Pharmacology and Experimental Therapeutics
Volume332
Issue number2
DOIs
Publication statusPublished - 2010 Feb
Externally publishedYes

Fingerprint

Lipopolysaccharides
Epithelial Cells
Macrophages
Inflammation
Caco-2 Cells
Tumor Necrosis Factor-alpha
Messenger RNA
Anti-Inflammatory Agents
Lipoxins
Arachidonic Acids
lipoxin A4
Cell Line
Peritoneal Macrophages
Intestinal Mucosa
Coculture Techniques
Unsaturated Fatty Acids
Interleukin-8
Cultured Cells
Colon
Phosphotransferases

ASJC Scopus subject areas

  • Pharmacology
  • Molecular Medicine

Cite this

Lipoxin A4 reduces lipopolysaccharide-induced inflammation in macrophages and intestinal epithelial cells through inhibition of nuclear factor-κB activation. / Kure, Izumi; Nishiumi, Shin; Nishitani, Yosuke; Tanoue, Takeshi; Ishida, Tsukasa; Mizuno, Masashi; Fujita, Tsuyoshi; Kutsumi, Hiromu; Arita, Makoto; Azuma, Takeshi; Yoshida, Masaru.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 332, No. 2, 02.2010, p. 541-548.

Research output: Contribution to journalArticle

Kure, Izumi ; Nishiumi, Shin ; Nishitani, Yosuke ; Tanoue, Takeshi ; Ishida, Tsukasa ; Mizuno, Masashi ; Fujita, Tsuyoshi ; Kutsumi, Hiromu ; Arita, Makoto ; Azuma, Takeshi ; Yoshida, Masaru. / Lipoxin A4 reduces lipopolysaccharide-induced inflammation in macrophages and intestinal epithelial cells through inhibition of nuclear factor-κB activation. In: Journal of Pharmacology and Experimental Therapeutics. 2010 ; Vol. 332, No. 2. pp. 541-548.
@article{5228a698cd0d48e8874dd670f5dcd911,
title = "Lipoxin A4 reduces lipopolysaccharide-induced inflammation in macrophages and intestinal epithelial cells through inhibition of nuclear factor-κB activation",
abstract = "Lipoxins, which are bioactive lipids derived from ω-6 polyunsaturated fatty acids, play important roles in various biological functions. In this study, the anti-inflammatory effects of lipoxin A4 (LXA4; 5S,6R,15Strihydroxy-7,9,13-trans-11-eicosatetraenoic acid) were investigated in in vitro cultured cell experiments and in vivo animal experiments. In mouse peritoneal macrophages and mouse macrophage cell line RAW264.7 cells, LXA4 reduced the lipopolysaccharide (LPS)-induced increase in the mRNA expression level of tumor necrosis factor (TNF)-α. LXA4 also reduced the LPS-induced nuclear translocation of nuclear factor-κB (NF-κB). In an LPS-induced acute inflammation mouse model, the injection of LXA4 at 5 μg/kg b.wt. led to down-regulation of the TNF-α level in serum and the TNF-α mRNA expression level in intestinal epithelial cells. Moreover, LXA4 reduced the LPS-caused phosphorylation of IκB kinases, IκB, and NF-κB, the degradation of IκB, and the nuclear translocation of NF-κB in intestinal epithelial cells. In a coculture system using RAW264.7 cells and human colon carcinoma cell line Caco-2 cells, treatment with LXA4 to Caco-2 cells led to reduction of LPS-evoked TNF-α production in RAW264.7 cells and interleukin-8 mRNA expression in Caco-2 cells. These results indicate that LXA4 exerts anti-inflammatory effects through inhibition of NF-κB activation, and, therefore, LXA4 may be useful as a therapeutic strategy against intestinal mucosa inflammation.",
author = "Izumi Kure and Shin Nishiumi and Yosuke Nishitani and Takeshi Tanoue and Tsukasa Ishida and Masashi Mizuno and Tsuyoshi Fujita and Hiromu Kutsumi and Makoto Arita and Takeshi Azuma and Masaru Yoshida",
year = "2010",
month = "2",
doi = "10.1124/jpet.109.159046",
language = "English",
volume = "332",
pages = "541--548",
journal = "Journal of Pharmacology and Experimental Therapeutics",
issn = "0022-3565",
publisher = "American Society for Pharmacology and Experimental Therapeutics",
number = "2",

}

TY - JOUR

T1 - Lipoxin A4 reduces lipopolysaccharide-induced inflammation in macrophages and intestinal epithelial cells through inhibition of nuclear factor-κB activation

AU - Kure, Izumi

AU - Nishiumi, Shin

AU - Nishitani, Yosuke

AU - Tanoue, Takeshi

AU - Ishida, Tsukasa

AU - Mizuno, Masashi

AU - Fujita, Tsuyoshi

AU - Kutsumi, Hiromu

AU - Arita, Makoto

AU - Azuma, Takeshi

AU - Yoshida, Masaru

PY - 2010/2

Y1 - 2010/2

N2 - Lipoxins, which are bioactive lipids derived from ω-6 polyunsaturated fatty acids, play important roles in various biological functions. In this study, the anti-inflammatory effects of lipoxin A4 (LXA4; 5S,6R,15Strihydroxy-7,9,13-trans-11-eicosatetraenoic acid) were investigated in in vitro cultured cell experiments and in vivo animal experiments. In mouse peritoneal macrophages and mouse macrophage cell line RAW264.7 cells, LXA4 reduced the lipopolysaccharide (LPS)-induced increase in the mRNA expression level of tumor necrosis factor (TNF)-α. LXA4 also reduced the LPS-induced nuclear translocation of nuclear factor-κB (NF-κB). In an LPS-induced acute inflammation mouse model, the injection of LXA4 at 5 μg/kg b.wt. led to down-regulation of the TNF-α level in serum and the TNF-α mRNA expression level in intestinal epithelial cells. Moreover, LXA4 reduced the LPS-caused phosphorylation of IκB kinases, IκB, and NF-κB, the degradation of IκB, and the nuclear translocation of NF-κB in intestinal epithelial cells. In a coculture system using RAW264.7 cells and human colon carcinoma cell line Caco-2 cells, treatment with LXA4 to Caco-2 cells led to reduction of LPS-evoked TNF-α production in RAW264.7 cells and interleukin-8 mRNA expression in Caco-2 cells. These results indicate that LXA4 exerts anti-inflammatory effects through inhibition of NF-κB activation, and, therefore, LXA4 may be useful as a therapeutic strategy against intestinal mucosa inflammation.

AB - Lipoxins, which are bioactive lipids derived from ω-6 polyunsaturated fatty acids, play important roles in various biological functions. In this study, the anti-inflammatory effects of lipoxin A4 (LXA4; 5S,6R,15Strihydroxy-7,9,13-trans-11-eicosatetraenoic acid) were investigated in in vitro cultured cell experiments and in vivo animal experiments. In mouse peritoneal macrophages and mouse macrophage cell line RAW264.7 cells, LXA4 reduced the lipopolysaccharide (LPS)-induced increase in the mRNA expression level of tumor necrosis factor (TNF)-α. LXA4 also reduced the LPS-induced nuclear translocation of nuclear factor-κB (NF-κB). In an LPS-induced acute inflammation mouse model, the injection of LXA4 at 5 μg/kg b.wt. led to down-regulation of the TNF-α level in serum and the TNF-α mRNA expression level in intestinal epithelial cells. Moreover, LXA4 reduced the LPS-caused phosphorylation of IκB kinases, IκB, and NF-κB, the degradation of IκB, and the nuclear translocation of NF-κB in intestinal epithelial cells. In a coculture system using RAW264.7 cells and human colon carcinoma cell line Caco-2 cells, treatment with LXA4 to Caco-2 cells led to reduction of LPS-evoked TNF-α production in RAW264.7 cells and interleukin-8 mRNA expression in Caco-2 cells. These results indicate that LXA4 exerts anti-inflammatory effects through inhibition of NF-κB activation, and, therefore, LXA4 may be useful as a therapeutic strategy against intestinal mucosa inflammation.

UR - http://www.scopus.com/inward/record.url?scp=76749095849&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=76749095849&partnerID=8YFLogxK

U2 - 10.1124/jpet.109.159046

DO - 10.1124/jpet.109.159046

M3 - Article

VL - 332

SP - 541

EP - 548

JO - Journal of Pharmacology and Experimental Therapeutics

JF - Journal of Pharmacology and Experimental Therapeutics

SN - 0022-3565

IS - 2

ER -