Glucocorticoid-Induced Leucine Zipper Is Protective in Th1-Mediated Models of Colitis

被引:102
作者
Cannarile, Lorenza [2 ]
Cuzzocrea, Salvatore [1 ,3 ]
Santucci, Luca [4 ]
Agostini, Massimiliano [2 ]
Mazzon, Emanuela [3 ]
Esposito, Emanuela [3 ,5 ]
Muia, Carmelo [1 ]
Coppo, Maddalena [2 ]
Di Paola, Rosanna [3 ]
Riccardi, Carlo [2 ]
机构
[1] Univ Messina, Sch Med, Dept Clin & Expt Med & Pharmacol, Messina, Italy
[2] Univ Perugia, Dept Clin & Expt Med, Sect Pharmacol & Polo Sci & Didatt Terni, I-06100 Perugia, Italy
[3] IRCCS Ctr Neurolesi Bonino Pulejo, Messina, Italy
[4] Azienda Osped Perugia, Perugia, Italy
[5] Univ Naples Federico II, Dept Expt Pharmacol, Naples, Italy
关键词
NF-KAPPA-B; INFLAMMATORY-BOWEL-DISEASE; T-CELL ACTIVATION; APOPTOSIS; IMMUNE; GENE; TRANSCRIPTION; INHIBITION; EXPRESSION; MICE;
D O I
10.1053/j.gastro.2008.09.024
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Background & Aims: Inflammatory bowel diseases are relatively common diseases of the gastrointestinal tract. The relative therapeutic efficacy of glucocorticoids used in inflammatory bowel diseases resides in part in their capability to inhibit activity of nuclear factor kappa B (NF-kappa B), a transcription factor central to the inflammatory process, and the consequent production of T-helper 1 (Th1)-type cytokines. Previous studies indicate that increased expression in transgenic mice of glucocorticoid-induced leucine zipper (GILZ), a gene rapidly induced by glucocorticoids, inhibits NF-kappa B and Th1 activity. Methods: We performed experiments with the aim to test the susceptibility of GILZ transgenic (GILZ-TG) mice to dinitrobenzene sulfonic acid-induced colitis. Results: Consistent with a decreased Th1 response, GILZ-TG mice were less susceptible to colitis induction as compared with wild-type littermates, while they were more susceptible to Th2-mediated colitis. The inhibition was comparable to that obtained with dexamethasone treatment. Moreover, diminished intestinal tissue damage, associated with inhibition of NF-kappa B nuclear translocation, interferon-gamma, tumor necrosis factor-alpha, and interleukin-1 production in CD4(+) T lymphocytes of the lamina propria, was evident in GILZ-TG as compared with wild-type mice. In addition, inhibition of colitis development was also evident when GILZ fusion protein was delivered in vivo in dinitrobenzene sulfonic acid-treated WT animals as well as in interleukin-10 knockout mice. Conclusions: Together these results demonstrate that GILZ mimics the effects of glucocorticoids, suggesting a contribution of this protein to the and-inflammatory activity of glucocorticoids in Th1-induced colitis.
引用
收藏
页码:530 / 541
页数:12
相关论文
共 37 条
[1]   Effects of steroid treatment on activation of nuclear factor κB in patients with inflammatory bowel disease [J].
Ardite, E ;
Panés, J ;
Miranda, M ;
Salas, A ;
Elizalde, JI ;
Sans, M ;
Arce, Y ;
Bordas, JM ;
Fernández-Checa, JC ;
Piqué, JM .
BRITISH JOURNAL OF PHARMACOLOGY, 1998, 124 (03) :431-433
[2]   Modulation of T-cell activation by the glucocorticoid-induced leucine zipper factor via inhibition of nuclear factor κB [J].
Ayroldi, E ;
Migliorati, G ;
Bruscoli, S ;
Marchetti, C ;
Zollo, O ;
Cannarile, L ;
D'Adamio, F ;
Riccardi, C .
BLOOD, 2001, 98 (03) :743-753
[3]   GILZ mediates the antiproliferative activity of glucocorticoids by negative regulation of Ras signaling [J].
Ayroldi, Emira ;
Zollo, Ornella ;
Bastianelli, Alessandra ;
Marchetti, Cristina ;
Agostini, Massimiliano ;
Di Virgilio, Rosa ;
Riccardi, Carlo .
JOURNAL OF CLINICAL INVESTIGATION, 2007, 117 (06) :1605-1615
[4]   Oxazolone colitis: A murine model of T helper cell type 2 colitis treatable with antibodies to interleukin 4 [J].
Boirivant, M ;
Fuss, IJ ;
Chu, A ;
Strober, W .
JOURNAL OF EXPERIMENTAL MEDICINE, 1998, 188 (10) :1929-1939
[5]   The immunological and genetic basis of inflammatory bowel disease [J].
Bouma, G ;
Strober, W .
NATURE REVIEWS IMMUNOLOGY, 2003, 3 (07) :521-533
[6]   Genomic and non-genomic effects of different glucocorticoids on mouse thymocyte apoptosis [J].
Bruscoli, S ;
Di Virgilio, R ;
Donato, V ;
Velardi, E ;
Baldoni, M ;
Marchetti, C ;
Migliorati, G ;
Riccardi, C .
EUROPEAN JOURNAL OF PHARMACOLOGY, 2006, 529 (1-3) :63-70
[7]   Infectious susceptibility and severe deficiency of leukocyte rolling and recruitment in E-selectin and P-selectin double mutant mice [J].
Bullard, DC ;
Kunkel, EJ ;
Kubo, H ;
Hicks, MJ ;
Lorenzo, I ;
Doyle, NA ;
Doerschuk, CM ;
Ley, K ;
Beaudet, AL .
JOURNAL OF EXPERIMENTAL MEDICINE, 1996, 183 (05) :2329-2336
[8]   Increased GILZ expression in transgenic mice up-regulates Th-2 lymphokines [J].
Cannarile, L ;
Fallarino, F ;
Agostini, M ;
Cuzzocrea, S ;
Mazzon, E ;
Vacca, C ;
Genovese, T ;
Migliorati, G ;
Ayroldi, E ;
Riccardi, C .
BLOOD, 2006, 107 (03) :1039-1047
[9]   Role of glucocorticoid-induced TNF receptor family gene (GITR) in collagen-induced arthritis [J].
Cuzzocrea, S ;
Ayroldi, E ;
Di Paola, R ;
Agostini, M ;
Mazzon, E ;
Bruscoli, S ;
Genovese, T ;
Ronchetti, S ;
Caputi, AP ;
Riccardi, C .
FASEB JOURNAL, 2005, 19 (10) :1253-1265
[10]   A new dexamethasone-induced gene of the leucine zipper family protects T lymphocytes from TCR/CD3-activated cell death [J].
D'Adamio, F ;
Zollo, O ;
Moraca, R ;
Ayroldi, E ;
Bruscoli, S ;
Bartoli, A ;
Cannarile, L ;
Migliorati, G ;
Riccardi, C .
IMMUNITY, 1997, 7 (06) :803-812