Peroxisome proliferator-activated receptor (PPAR) γ:: a new target for the treatment of inflammatory bowel disease

被引:0
作者
Dubuquoy, L
Bourdon, C
Peuchmaur, M
Leibowitz, MD
Nutten, S
Colombel, JF
Auwerx, J
Desreumaux, P
机构
[1] CHU Lille, Lab Rech Malad Inflammatoires Intestinales, F-59037 Lille, France
[2] Inst Pasteur, LBRE, F-59019 Lille, France
[3] Hop Robert Debre, Serv Anat & Cytol Pathol, F-75019 Paris, France
[4] Ligand Pharmaceut, San Diego, CA USA
[5] Inst Genet & Biol Mol & Cellulaire, Illkirch Graffenstaden, France
来源
GASTROENTEROLOGIE CLINIQUE ET BIOLOGIQUE | 2000年 / 24卷 / 8-9期
关键词
inflammatory bowel diseases; nuclear receptors; PPAR gamma; cytokines; therapeutic research;
D O I
暂无
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
The peroxisome proliferator-activated receptor (PPAR) gamma is highly expressed in the colon mucosa. In vitro, it regulates inflammation. Aim - To evaluate the anti-inflammatory functions of PPAR gamma agonist during a trinitrobenzene sulfonic acid (TNBS)-induced colitis in mice. Methods - Colitis was induced in Balb/c mice after intra-rectal administration of TNBS. The intensity of inflammation was assessed 2 and 5 days after colitis induction by macroscopic and histologic scores and by the quantification of colon myeloperoxidase (MPO), IL-1 beta and TNF alpha mRNA concentrations. The therapeutic role of PPAR gamma agonist given by oral gavage was assessed in preventive and treatment modes. Results - TNBS induced severe macroscopic and histologic lesions, with high mucosal MPO, IL-1 beta and TNF alpha mRNA concentrations. PPAR gamma agonist given preventively or in treatment mode allowed a significant decrease of macroscopic and histologic scores through a normalization of MPO, IL-1 beta and TNF alpha mRNA concentrations. Conclusion - PPAR gamma agonist decreases the intensity of TNBS induced colitis through normalization of IL-1 beta and TNF alpha expression. PPAR gamma agonists may be proposed as new therapeutic agents in inflammatory bowel diseases.
引用
收藏
页码:719 / 724
页数:6
相关论文
共 29 条
[1]   Prophylactic effect of dietary glutamine supplementation on interleukin 8 and tumour necrosis factor alpha production in trinitrobenzene sulphonic acid induced colitis [J].
Ameho, CK ;
Adjei, AA ;
Harrison, EK ;
Takeshita, K ;
Morioka, T ;
Arakaki, Y ;
Ito, E ;
Suzuki, I ;
Kulkarni, AD ;
Kawajiri, A ;
Yamamoto, S .
GUT, 1997, 41 (04) :487-493
[2]   Novel peroxisome proliferator-activated receptor (PPAR) γ and PPARδ ligands produce distinct biological effects [J].
Berger, J ;
Leibowitz, MD ;
Doebber, TW ;
Elbrecht, A ;
Zhang, B ;
Zhou, GC ;
Biswas, C ;
Cullinan, CA ;
Hayes, NS ;
Li, Y ;
Tanen, M ;
Ventre, J ;
Wu, MS ;
Berger, GD ;
Mosley, R ;
Marquis, R ;
Santini, C ;
Sahoo, SP ;
Tolman, RL ;
Smith, RG ;
Moller, DE .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (10) :6718-6725
[3]   Distinct cytokine patterns in early and chronic ileal lesions of Crohn's disease [J].
Desreumaux, P ;
Brandt, E ;
Gambiez, L ;
Emilie, D ;
Geboes, K ;
Klein, O ;
Ectors, N ;
Cortot, A ;
Capron, M ;
Colombel, JF .
GASTROENTEROLOGY, 1997, 113 (01) :118-126
[4]  
Desreumaux P, 1999, GASTROEN CLIN BIOL, V23, pB159
[5]   T-HELPER TYPE 1/T HELPER TYPE-2 CYTOKINES AND T-CELL DEATH - PREVENTIVE EFFECT OF INTERLEUKIN-12 ON ACTIVATION-INDUCED AND CD95 (FAS/APO-1)-MEDIATED APOPTOSIS OF CD4(+) T-CELLS FROM HUMAN IMMUNODEFICIENCY VIRUS-INFECTED PERSONS [J].
ESTAQUIER, J ;
IDZIOREK, T ;
ZOU, WP ;
EMILIE, D ;
FARBER, CM ;
BOUREZ, JM ;
AMEISEN, JC .
JOURNAL OF EXPERIMENTAL MEDICINE, 1995, 182 (06) :1759-1767
[6]   The organization, promoter analysis, and expression of the human PPAR gamma gene [J].
Fajas, L ;
Auboeuf, D ;
Raspe, E ;
Schoonjans, K ;
Lefebvre, AM ;
Saladin, R ;
Najib, J ;
Laville, M ;
Fruchart, JC ;
Deeb, S ;
VidalPuig, A ;
Flier, J ;
Briggs, MR ;
Staels, B ;
Vidal, H ;
Auwerx, J .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (30) :18779-18789
[7]   15-DEOXY-DELTA(12,14)-PROSTAGLANDIN J(2) IS A LIGAND FOR THE ADIPOCYTE DETERMINATION FACTOR PPAR-GAMMA [J].
FORMAN, BM ;
TONTONOZ, P ;
CHEN, J ;
BRUN, RP ;
SPIEGELMAN, BM ;
EVANS, RM .
CELL, 1995, 83 (05) :803-812
[8]  
Hafraoui S, 1999, GASTROENTEROLOGY, V116, pA689
[9]   Increased expression of transforming growth factor alpha precursors in acute experimental colitis in rats [J].
Hoffmann, P ;
Zeeh, JM ;
Lakshmanan, J ;
Wu, VS ;
Procaccino, F ;
Reinshagen, M ;
McRoberts, JA ;
Eysselein, VE .
GUT, 1997, 41 (02) :195-202
[10]   The mechanism of altered neural function in a rat model of acute colitis [J].
Jacobson, K ;
McHugh, K ;
Collins, SM .
GASTROENTEROLOGY, 1997, 112 (01) :156-162