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Cuzzocrea, S. et al.

Cuzzocrea, Nocentini, Di Paola, Agostini, Mazzon, Ronchetti, Crisafulli, Esposito, Caputi, Riccardi,

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

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.[1]

References

Proinflammatory role of glucocorticoid-induced TNF receptor-related gene in acute lung inflammation. Cuzzocrea, S., Nocentini, G., Di Paola, R., Agostini, M., Mazzon, E., Ronchetti, S., Crisafulli, C., Esposito, E., Caputi, A.P., Riccardi, C. J. Immunol. (2006) [Pubmed]

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