过氧化物酶体增殖物激活受体与溃疡性结肠炎
周静平, 邓长生, 武汉大学中南医院消化内科 湖北省武汉市 430071
通讯作者: 周静平,430071, 湖北省武汉市武昌东湖路169号, 武汉大学中南医院消化内科. jingping714@yahoo.com.cn
电话: 027-87331114
收稿日期: 2005-03-01 接受日期: 2005-03-21
摘要过氧化物酶体增殖物激活受体(peroxisome proliferator-activated receptors，PPARs)是新近发现的一类核转录因子，属Ⅱ型核受体超家族，被相应的配体激活后调节目的基因转录，在脂代谢、糖代谢、细胞增殖分化等方面发挥作用.近年来研究证实，PPARs参与炎症及免疫反应的调节，与溃疡性结肠炎关系密切，其配体有望成为新一代治疗溃疡性结肠炎的药物.
, 百拇医药
周静平, 邓长生. 过氧化物酶体增殖物激活受体与溃疡性结肠炎. 世界华人消化杂志 2005;13(8):1011-10131 Dubuquoy L, Jansson EA, Deeb S, Rakotobe S, Karoui M, Colombel JF, Auwerx J, Pettersson S, Desreumaux P.
Impaired expression of peroxisome proliferator-activated receptor g in ulcerative colitis. Gastroenterology
2003;124:1265-1276
2 Su CG, Wen XM, Bailey ST, Jiang W, Rangwala SM, Keibaugh SA, Flanigan A, Murthy S, Lazar MA, Wu GD. A novel
, 百拇医药
therapy for colitis utilizing PPAR-g ligands to inhibit the epithelial inflammatory response. J Clin Invest 1999;104:383-389
3 Desreumaux P, Dubuquoy L, Nutten S, Peuchmaur M, Englaro W, Schooljans K, Derijard B, Desvergne B, Wahli W,Chambon P, Leibowitz MD, Colombel JF, Auwerx J. Attenuation of colon inflammation through activators of the
Retinoid X Receptor(RXR)/Peroxisome Proliferator-activated Receptor g(PPARg)heterodimer: a basis for new
, 百拇医药
therapeutic strategies. J Exp Med 2001;193:827-838
4 Bassaganya-Riera J, Reynolds K, Martino-Catt S, Cui YZ, Hennighausen L, Gonzalez F, Rohrer J, Benninghoff AU,Hontecillas R. Activation of PPARg and d by conjugated linoleic acid mediates protection from experimental inflammatory
bowel disease. Gastroenterology 2004;127:777-791
5 Auboeuf D, Rieusset J, Fajas L, Vallier P, Frering V, Riou JP, Staels B, Auwerx J, Laville M, Vidal H. Tissue distribution
, 百拇医药
and quantification of the expression of mRNAs of peroxisome proliferator-activated receptors and liver X receptor-a
in human. Diabetes 1997;46:1319-1327
6 Gelman L, Fruchart LC, Auwerx J. An update on the mechanisms of action of the peroxisome proliferator-activated
receptors (PPARs) and their roles in inflammtion and cancer. Cell Mol Life Sci 1999;55:932-943
, 百拇医药
7 Cipolla G, Crema F, Sacco S, Moro E, De Point F, Frigo G. Nonsteroidal anti-inflammatory drugs and inflammatory
bowel disease:current perspectives. Pharmacol Res 2002;46:1-6
8 Vamecq J, Latruffe N. Medical significance of peroxisome proliferator-activated receptors. Lancet 1999;354:141-148
9 Kinoshita M, Suzuki Y, Saito Y. Butyrate reduces colonic paracellular permeability by enhancing PPARg acitivation.
, 百拇医药
Biochem BiophysRes Commu 2002;293:827-831
10 Blanquart C, Barbier O, Fruchart JC, Staels B, Glineur C. Peroxisome proliferator-activated receptors:regulation
of transcripitional acitivities and roles in inflammtion. J Steroid Biochem Mol Biol 2003;85:267-273
11 Devchand PR, Keller H, Peters JM, Vazquez M, Gonzalesz FJ, Wahli W. The PPARa-leukotriene B4 pathway to
, 百拇医药
inflammation control. Nature 1996;384:39-43
12 Gan XD, Wong B, Wright SD, Cai TQ. Production of matrix metalloproteinase-9 in CaCo-2 cell in response to
inflammatory stimuli. J Interferon Cytokine Res 2001;21:93-98
13 Shu H, Wong B, Zhou G, Li Y, Berger J, Woods JW, Wright SD, Cai TQ. Activation of PPARa or g reduces sectetion
of matrix metalloproteinase 9 but not interleukin 8 from human monocytic THP-1 cells. Biochem Biophys Res Commu
, 百拇医药
2000;267:345-349
14 Clark RB, Bishop-Bailey D, Estrada-Hernandez T, Hla T, Puddington L, Padula SJ. The nuclear receptor PPARg and
immunoregulation: PPARg mediates inhibition of helper T cell responses. J Immunol 2000;164:1364-1371
15 Faveeuw C, Fougeray S, Angeli V, Fontaine J, Chinetti G, Gosset P, Delerive P, Maliszewski C, Capron M, Staels B,Moser M, Trottein F. Peroxisome proliferator-activated receptor g activators inhibit interleukin-12 production in
, 百拇医药
murine dendritic cells. FEBS Lett 2000;486:261-266
16 Meier CA, Chicheportiche R, Juge-Aubry CE, Dreyer MG, Dayer JM. Regulation of the interleukin-1 receptor antagonist
in THP-1 cells by ligands of the peroxisome proliferator-activated receptor g. Cytokine 2002;18:320-328
17 Katayama K, Wada K, Nakajima A, Mizuguchi H, Hayakawa T, Nakagawa S, Kadowaki T, Nafai R, Kamisaki Y,Blumaerg RS, Mayumi T. A novel PPARg gene therapy to control inflammation associated with inflammatory bowel
, http://www.100md.com
disease in a murine model. Gastroenterology 2003;124:1315-1324
18 Cuzzocrea S, Pisano B, Dugo L, Ianaro A, Maffia P, Patel NSA, Paola RD, Ialenti A, Genovese T, Chatterjee PK,Rosa MD, Caputi AP, Thiemermann C. Rosiglitazone, a ligand of the peroxisome proliferator- activated receptor-g,reduces acute inflammtion. Eur J Pharmacol 2004;483:79-93
19 Nakajima A, Wada K, Miki H, Kubota N, Nakajima N, Terauchi Y, Ohnishi S, Saubermann LJ, Kadowaki T,Blumaerg RS, Nagai R, Matsuhashi N. Endogenous PPARg mediates anti- inflammtory activity in murine
, 百拇医药
ischemia-reperfusion injury. Gastroenterology 2001;120:460-469
20 Chinetti G, Fruchart JC, Staels B. Peroxisome proliferator-activated receptors (PPARs): nuclear receptors at the
crossroads between lipid metabolism and inflammtion. Inflamm Res 2000;49:497-505
21 Auwerx J. Nuclear receptors I. PPARg in the gastrointestinal tract:gain or pain?
Am J PhysiolGastrointest Liver Physiol 2002;282:581-585
, 百拇医药
22 邓长生, 夏冰. 炎症性肠病. 第1版. 北京: 人民卫生出版社, 1998:131-145
23 Saubermann LJ, Nakajima A, Wada K, Zhao S, Terauchi Y, Kadowaki T, Aburatani H, Matsuhashi N, Nagai R,Blumberg RS. Perxisome proliferator-activated receptor gamma agonist ligands stimulate a Th2 cytokine response
and prevent acute colitis. Inflamm Bowel Dis 2002;8:330-339
24 Wu GD. Is there a roles for PPARg in IBD? Yes, no, maybe. Gastroenterology 2003;124:1538-1542
, 百拇医药
25 Wachtershauser A, Loitsch SM, Stein J. PPAR-g is selectively upregulated in Caco-2 cells by butyrate.
Biochem Biophys Res Commu 2000;272:380-385
26 Cuzzocrea S, Di Paola R, Mazzon E, Genvese T, Muia C, Centorrino T, Caputi AP. Role of endogenous and exogenous
ligands for the peroxisome proliferators activated receptors alpha(PPAR-a)in the development of inflammatory bowel
disease in mice. Lab Invest 2004;84:1643-1654
编辑 张海宁, http://www.100md.com( 周静平,邓长生)
通讯作者: 周静平,430071, 湖北省武汉市武昌东湖路169号, 武汉大学中南医院消化内科. jingping714@yahoo.com.cn
电话: 027-87331114
收稿日期: 2005-03-01 接受日期: 2005-03-21
摘要过氧化物酶体增殖物激活受体(peroxisome proliferator-activated receptors，PPARs)是新近发现的一类核转录因子，属Ⅱ型核受体超家族，被相应的配体激活后调节目的基因转录，在脂代谢、糖代谢、细胞增殖分化等方面发挥作用.近年来研究证实，PPARs参与炎症及免疫反应的调节，与溃疡性结肠炎关系密切，其配体有望成为新一代治疗溃疡性结肠炎的药物.
, 百拇医药
周静平, 邓长生. 过氧化物酶体增殖物激活受体与溃疡性结肠炎. 世界华人消化杂志 2005;13(8):1011-10131 Dubuquoy L, Jansson EA, Deeb S, Rakotobe S, Karoui M, Colombel JF, Auwerx J, Pettersson S, Desreumaux P.
Impaired expression of peroxisome proliferator-activated receptor g in ulcerative colitis. Gastroenterology
2003;124:1265-1276
2 Su CG, Wen XM, Bailey ST, Jiang W, Rangwala SM, Keibaugh SA, Flanigan A, Murthy S, Lazar MA, Wu GD. A novel
, 百拇医药
therapy for colitis utilizing PPAR-g ligands to inhibit the epithelial inflammatory response. J Clin Invest 1999;104:383-389
3 Desreumaux P, Dubuquoy L, Nutten S, Peuchmaur M, Englaro W, Schooljans K, Derijard B, Desvergne B, Wahli W,Chambon P, Leibowitz MD, Colombel JF, Auwerx J. Attenuation of colon inflammation through activators of the
Retinoid X Receptor(RXR)/Peroxisome Proliferator-activated Receptor g(PPARg)heterodimer: a basis for new
, 百拇医药
therapeutic strategies. J Exp Med 2001;193:827-838
4 Bassaganya-Riera J, Reynolds K, Martino-Catt S, Cui YZ, Hennighausen L, Gonzalez F, Rohrer J, Benninghoff AU,Hontecillas R. Activation of PPARg and d by conjugated linoleic acid mediates protection from experimental inflammatory
bowel disease. Gastroenterology 2004;127:777-791
5 Auboeuf D, Rieusset J, Fajas L, Vallier P, Frering V, Riou JP, Staels B, Auwerx J, Laville M, Vidal H. Tissue distribution
, 百拇医药
and quantification of the expression of mRNAs of peroxisome proliferator-activated receptors and liver X receptor-a
in human. Diabetes 1997;46:1319-1327
6 Gelman L, Fruchart LC, Auwerx J. An update on the mechanisms of action of the peroxisome proliferator-activated
receptors (PPARs) and their roles in inflammtion and cancer. Cell Mol Life Sci 1999;55:932-943
, 百拇医药
7 Cipolla G, Crema F, Sacco S, Moro E, De Point F, Frigo G. Nonsteroidal anti-inflammatory drugs and inflammatory
bowel disease:current perspectives. Pharmacol Res 2002;46:1-6
8 Vamecq J, Latruffe N. Medical significance of peroxisome proliferator-activated receptors. Lancet 1999;354:141-148
9 Kinoshita M, Suzuki Y, Saito Y. Butyrate reduces colonic paracellular permeability by enhancing PPARg acitivation.
, 百拇医药
Biochem BiophysRes Commu 2002;293:827-831
10 Blanquart C, Barbier O, Fruchart JC, Staels B, Glineur C. Peroxisome proliferator-activated receptors:regulation
of transcripitional acitivities and roles in inflammtion. J Steroid Biochem Mol Biol 2003;85:267-273
11 Devchand PR, Keller H, Peters JM, Vazquez M, Gonzalesz FJ, Wahli W. The PPARa-leukotriene B4 pathway to
, 百拇医药
inflammation control. Nature 1996;384:39-43
12 Gan XD, Wong B, Wright SD, Cai TQ. Production of matrix metalloproteinase-9 in CaCo-2 cell in response to
inflammatory stimuli. J Interferon Cytokine Res 2001;21:93-98
13 Shu H, Wong B, Zhou G, Li Y, Berger J, Woods JW, Wright SD, Cai TQ. Activation of PPARa or g reduces sectetion
of matrix metalloproteinase 9 but not interleukin 8 from human monocytic THP-1 cells. Biochem Biophys Res Commu
, 百拇医药
2000;267:345-349
14 Clark RB, Bishop-Bailey D, Estrada-Hernandez T, Hla T, Puddington L, Padula SJ. The nuclear receptor PPARg and
immunoregulation: PPARg mediates inhibition of helper T cell responses. J Immunol 2000;164:1364-1371
15 Faveeuw C, Fougeray S, Angeli V, Fontaine J, Chinetti G, Gosset P, Delerive P, Maliszewski C, Capron M, Staels B,Moser M, Trottein F. Peroxisome proliferator-activated receptor g activators inhibit interleukin-12 production in
, 百拇医药
murine dendritic cells. FEBS Lett 2000;486:261-266
16 Meier CA, Chicheportiche R, Juge-Aubry CE, Dreyer MG, Dayer JM. Regulation of the interleukin-1 receptor antagonist
in THP-1 cells by ligands of the peroxisome proliferator-activated receptor g. Cytokine 2002;18:320-328
17 Katayama K, Wada K, Nakajima A, Mizuguchi H, Hayakawa T, Nakagawa S, Kadowaki T, Nafai R, Kamisaki Y,Blumaerg RS, Mayumi T. A novel PPARg gene therapy to control inflammation associated with inflammatory bowel
, http://www.100md.com
disease in a murine model. Gastroenterology 2003;124:1315-1324
18 Cuzzocrea S, Pisano B, Dugo L, Ianaro A, Maffia P, Patel NSA, Paola RD, Ialenti A, Genovese T, Chatterjee PK,Rosa MD, Caputi AP, Thiemermann C. Rosiglitazone, a ligand of the peroxisome proliferator- activated receptor-g,reduces acute inflammtion. Eur J Pharmacol 2004;483:79-93
19 Nakajima A, Wada K, Miki H, Kubota N, Nakajima N, Terauchi Y, Ohnishi S, Saubermann LJ, Kadowaki T,Blumaerg RS, Nagai R, Matsuhashi N. Endogenous PPARg mediates anti- inflammtory activity in murine
, 百拇医药
ischemia-reperfusion injury. Gastroenterology 2001;120:460-469
20 Chinetti G, Fruchart JC, Staels B. Peroxisome proliferator-activated receptors (PPARs): nuclear receptors at the
crossroads between lipid metabolism and inflammtion. Inflamm Res 2000;49:497-505
21 Auwerx J. Nuclear receptors I. PPARg in the gastrointestinal tract:gain or pain?
Am J PhysiolGastrointest Liver Physiol 2002;282:581-585
, 百拇医药
22 邓长生, 夏冰. 炎症性肠病. 第1版. 北京: 人民卫生出版社, 1998:131-145
23 Saubermann LJ, Nakajima A, Wada K, Zhao S, Terauchi Y, Kadowaki T, Aburatani H, Matsuhashi N, Nagai R,Blumberg RS. Perxisome proliferator-activated receptor gamma agonist ligands stimulate a Th2 cytokine response
and prevent acute colitis. Inflamm Bowel Dis 2002;8:330-339
24 Wu GD. Is there a roles for PPARg in IBD? Yes, no, maybe. Gastroenterology 2003;124:1538-1542
, 百拇医药
25 Wachtershauser A, Loitsch SM, Stein J. PPAR-g is selectively upregulated in Caco-2 cells by butyrate.
Biochem Biophys Res Commu 2000;272:380-385
26 Cuzzocrea S, Di Paola R, Mazzon E, Genvese T, Muia C, Centorrino T, Caputi AP. Role of endogenous and exogenous
ligands for the peroxisome proliferators activated receptors alpha(PPAR-a)in the development of inflammatory bowel
disease in mice. Lab Invest 2004;84:1643-1654
编辑 张海宁, http://www.100md.com( 周静平,邓长生)
