Pioglitazone, a PPAR-γ ligand, provides protection from dextran sulfate sodium-induced colitis in mice in association with inhibition of the NF-κB-cytokine cascade

被引:59
作者
Takagi, T [1 ]
Naito, Y [1 ]
Tomatsuri, N [1 ]
Handa, O [1 ]
Ichikawa, H [1 ]
Yoshida, N [1 ]
Yoshikawa, T [1 ]
机构
[1] Kyoto Prefectural Univ Med, Dept Med 1, Kamigyo Ku, Kyoto 6028566, Japan
关键词
D O I
10.1179/135100002125000802
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Nuclear factor-kappaB-dependent up-regulation of inflammatory cytokines occurs in inflammatory bowel disease. We investigated the effect of pioglitazone, a peroxisome proliferator-activated receptor-gamma ligand, on dextran sulfate sodium-induced colonic mucosal injury and inflammation in mice. Acute colitis was induced in female mice receiving 0, 1, 3, and 10 mg/kg i.p. of pioglitazone daily. Colonic mucosal inflammation was evaluated chemically and histologically. Thiobarbituric acid-reactive substances and tissue-associated myeloperoxidase activity were measured in intestinal mucosa as indices of lipid peroxidation and neutrophil infiltration, respectively. Colonic mRNA expression of pro-inflammatory cytokines and inducible nitric oxide synthase was measured by reverse transcription-PCR and nuclear factor-kappaB activation was evaluated by electrophoretic mobility shift assay. Dextran sulfate sodium administration resulted in decreases in body weight and colon length and increases in lipid peroxide and neutrophil accumulation of the intestine. In contrast, coadministration with pioglitazone prevented these changes. Transcripts coding for pro-inflammatory cytokines and inducible nitric oxide were expressed in high levels after the development of colitis, and pioglitazone markedly reduced mRNA expression of these genes. DNA binding activity of nuclear factor-kappaB was markedly increased, whereas in pioglitazone co-treated intestines the effect was significantly reduced. These data suggest that peroxisome proliferator-activated receptor-gamma may be a novel therapeutic target for the therapy of inflammatory bowel disease.
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页码:283 / 289
页数:7
相关论文
共 39 条
  • [1] Mechanisms of disease - Nuclear factor-kappa b - A pivotal transcription factor in chronic inflammatory diseases
    Barnes, PJ
    Larin, M
    [J]. NEW ENGLAND JOURNAL OF MEDICINE, 1997, 336 (15) : 1066 - 1071
  • [2] Intercellular adhesion molecule-1 expression in dextran sodium sulfate-induced colitis in rats
    Breider, MA
    Eppinger, M
    Gough, A
    [J]. VETERINARY PATHOLOGY, 1997, 34 (06) : 598 - 604
  • [3] Attenuation of colon inflammation through activators of the retinoid X receptor (RXR)/peroxisome proliferator-activated receptor γ (BPARγ) heterodimer:: A basis for new therapeutic strategies
    Desreumaux, P
    Dubuquoy, L
    Nutten, S
    Peuchmaur, M
    Englaro, W
    Schoonjans, K
    Derijard, B
    Desvergne, B
    Wahli, W
    Chambon, P
    Leibowitz, MD
    Colombel, JF
    Auwerx, J
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 2001, 193 (07) : 827 - 838
  • [4] Dijkstra G, 1998, J PATHOL, V186, P416, DOI 10.1002/(SICI)1096-9896(199812)186:4<416::AID-PATH201>3.0.CO
  • [5] 2-U
  • [6] XANTHINE-OXIDASE AND NEUTROPHIL INFILTRATION IN INTESTINAL ISCHEMIA
    GRISHAM, MB
    HERNANDEZ, LA
    GRANGER, DN
    [J]. AMERICAN JOURNAL OF PHYSIOLOGY, 1986, 251 (04): : G567 - G574
  • [7] Nuclear factor-κB activity and intestinal inflammation in dextran sulphate sodium (DSS)-induced colitis in mice is suppressed by gliotoxin
    Herfarth, H
    Brand, K
    Rath, HC
    Rogler, G
    Schölmerich, J
    Falk, W
    [J]. CLINICAL AND EXPERIMENTAL IMMUNOLOGY, 2000, 120 (01) : 59 - 65
  • [8] Role of active oxygen species and lipid peroxidation in mepirizole-induced duodenal ulcers in rats
    Iinuma, S
    Yoshikawa, T
    Yoshida, N
    Naito, Y
    Kondo, M
    [J]. DIGESTIVE DISEASES AND SCIENCES, 1998, 43 (08) : 1657 - 1664
  • [9] Peroxisome proliferator-activated receptor activators target human endothelial cells to inhibit leukocyte-endothelial cell interaction
    Jackson, SM
    Parhami, F
    Xi, XP
    Berliner, JA
    Hsueh, WA
    Law, RE
    Demer, LL
    [J]. ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 1999, 19 (09) : 2094 - 2104
  • [10] PPAR-γ agonists inhibit production of monocyte inflammatory cytokines
    Jiang, CY
    Ting, AT
    Seed, B
    [J]. NATURE, 1998, 391 (6662) : 82 - 86