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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Acute Disease
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Animals
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Carrageenan / administration & dosage
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Cell Membrane Permeability / genetics
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Cell Membrane Permeability / immunology
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Down-Regulation / genetics
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Down-Regulation / immunology
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Glucocorticoid-Induced TNFR-Related Protein
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Glucocorticoids / physiology*
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Inflammation / chemically induced
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Inflammation / enzymology
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Inflammation / genetics
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Inflammation / prevention & control
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Inflammation Mediators / antagonists & inhibitors
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Inflammation Mediators / metabolism
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Inflammation Mediators / physiology*
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Leukocyte Count
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Leukocytes / pathology
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Ligands
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Lung / immunology*
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Lung / metabolism
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Lung / pathology*
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Mice
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Mice, Knockout
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Neutrophil Infiltration / genetics
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Neutrophil Infiltration / immunology
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Pleural Effusion / chemically induced
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Pleural Effusion / enzymology
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Pleural Effusion / genetics
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Pleural Effusion / prevention & control
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Pleurisy / chemically induced
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Pleurisy / enzymology
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Pleurisy / genetics
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Pleurisy / prevention & control
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Receptors, Nerve Growth Factor / antagonists & inhibitors
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Receptors, Nerve Growth Factor / deficiency
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Receptors, Nerve Growth Factor / genetics*
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Receptors, Nerve Growth Factor / physiology*
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Receptors, Tumor Necrosis Factor / antagonists & inhibitors
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Receptors, Tumor Necrosis Factor / deficiency
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Receptors, Tumor Necrosis Factor / genetics*
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Receptors, Tumor Necrosis Factor / physiology*
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Tumor Necrosis Factors / biosynthesis
Substances
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Glucocorticoid-Induced TNFR-Related Protein
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Glucocorticoids
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Inflammation Mediators
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Ligands
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Receptors, Nerve Growth Factor
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Receptors, Tumor Necrosis Factor
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Tnfrsf18 protein, mouse
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Tnfsf18 protein, mouse
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Tumor Necrosis Factors
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Carrageenan