Proinflammatory role of glucocorticoid-induced TNF receptor-related gene in acute lung inflammation.

Abstract

Glucocorticoid-induced TNFR-related gene (GITR) participates in the immune/inflammatory response. Because GITR expression has been described in cells other than T lymphocytes, we investigated whether it also modulates acute inflammatory response. Using GITR-deficient (GITR(-/-)) mice, we analyzed the role of GITR in the development of carrageenan-induced lung inflammation (pleurisy) by studying several proinflammatory markers 2-8 h after carrageenan injection. When compared with GITR(+/+), GITR(-/-) mice exhibited decreased production of turbid exudate containing a lower number of leukocytes. This was correlated with the reduction of inflammatory markers (including TNF-alpha, IL-1beta, myeloperoxidase, inducible NO synthase, and cyclooxygenase 2) in the pleural exudate and/or in the lung. Moreover, endothelial cells expressed lower levels of adhesion molecules. In lungs of GITR(+/+) mice, GITR ligand expression was not modulated during pleurisy, while that of GITR increased, as a consequence of increased infiltration by GITR-expressing cells and of GITR up-regulation in macrophages and endothelial cells. Finally, cotreatment of GITR(+/+) mice with carrageenan and Fc-GITR fusion protein decreased the number of inflammatory cells (pleural macrophages and lung neutrophils) as compared with carrageenan treatment alone, confirming that GITR plays a role in the modulation of pleurisy.

• Authors: Salvatore Cuzzocrea, Giuseppe Nocentini, Rosanna Di Paola, Massimiliano Agostini, Emanuela Mazzon, Simona Ronchetti, Concetta Crisafulli, Emanuela Esposito, Achille P Caputi, Carlo Riccardi
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 177 Issue 1 Pg. 631-41 (Jul 01 2006) ISSN: 0022-1767 [Print] United States
• PMID: 16785561 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Glucocorticoid-Induced TNFR-Related Protein
• Glucocorticoids
• Inflammation Mediators
• Ligands
• Receptors, Nerve Growth Factor
• Receptors, Tumor Necrosis Factor
• Tnfrsf18 protein, mouse
• Tnfsf18 protein, mouse
• Tumor Necrosis Factors
• Carrageenan

Topics

• Acute Disease
• Animals
• Carrageenan (administration & dosage)
• Cell Membrane Permeability (genetics, immunology)
• Down-Regulation (genetics, immunology)
• Glucocorticoid-Induced TNFR-Related Protein
• Glucocorticoids (physiology)
• Inflammation (chemically induced, enzymology, genetics, prevention & control)
• Inflammation Mediators (antagonists & inhibitors, metabolism, physiology)
• Leukocyte Count
• Leukocytes (pathology)
• Ligands
• Lung (immunology, metabolism, pathology)
• Mice
• Mice, Knockout
• Neutrophil Infiltration (genetics, immunology)
• Pleural Effusion (chemically induced, enzymology, genetics, prevention & control)
• Pleurisy (chemically induced, enzymology, genetics, prevention & control)
• Receptors, Nerve Growth Factor (antagonists & inhibitors, deficiency, genetics, physiology)
• Receptors, Tumor Necrosis Factor (antagonists & inhibitors, deficiency, genetics, physiology)
• Tumor Necrosis Factors (biosynthesis)