Glucocorticoid-induced leucine zipper is protective in Th1-mediated models of colitis.

Abstract

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 kappaB (NF-kappaB), 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-kappaB 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-kappaB 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 anti-inflammatory activity of glucocorticoids in Th1-induced colitis.

• Authors: Lorenza Cannarile, Salvatore Cuzzocrea, Luca Santucci, Massimiliano Agostini, Emanuela Mazzon, Emanuela Esposito, Carmelo Muià, Maddalena Coppo, Rosanna Di Paola, Carlo Riccardi
• Journal: Gastroenterology (Gastroenterology) Vol. 136 Issue 2 Pg. 530-41 (Feb 2009) ISSN: 1528-0012 [Electronic] United States
• PMID: 18996377 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Dsip1 protein, mouse
• Glucocorticoids
• Interleukin-1
• NF-kappa B
• Transcription Factors
• Tumor Necrosis Factor-alpha
• Intercellular Adhesion Molecule-1
• 2,4-dinitrofluorobenzene sulfonic acid
• Oxazolone
• Interferon-gamma
• Dinitrofluorobenzene

Topics

• Animals
• Colitis (chemically induced, metabolism, pathology)
• Colon (metabolism, pathology)
• Dinitrofluorobenzene (analogs & derivatives)
• Disease Models, Animal
• Genetic Predisposition to Disease
• Glucocorticoids (pharmacology)
• Intercellular Adhesion Molecule-1 (metabolism)
• Interferon-gamma (metabolism)
• Interleukin-1 (metabolism)
• Leucine Zippers (drug effects)
• Mice
• Mice, Knockout
• Mice, Transgenic
• NF-kappa B (metabolism)
• Oxazolone
• Th1 Cells (metabolism, pathology)
• Th2 Cells (metabolism, pathology)
• Transcription Factors (genetics, metabolism)
• Tumor Necrosis Factor-alpha (metabolism)