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

Salvatore Cuzzocrea, Giuseppe Nocentini, Rosanna Di Paola, Massimiliano Agostini, Emanuela Mazzon, Simona Ronchetti, Concetta Crisafulli, Emanuela Esposito, Achille P. Caputi, Carlo Riccardi

Research output: Contribution to journalArticlepeer-review

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-α, IL-1β, 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.

Original languageEnglish
Pages (from-to)631-641
Number of pages11
JournalJournal of Immunology
Volume177
Issue number1
Publication statusPublished - Jul 1 2006

ASJC Scopus subject areas

  • Immunology

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