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 language | English |
|---|---|
| Pages (from-to) | 631-641 |
| Number of pages | 11 |
| Journal | Journal of Immunology |
| Volume | 177 |
| Issue number | 1 |
| Publication status | Published - Jul 1 2006 |
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- Immunology
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Proinflammatory role of glucocorticoid-induced TNF receptor-related gene in acute lung inflammation. / Cuzzocrea, Salvatore; Nocentini, Giuseppe; Di Paola, Rosanna; Agostini, Massimiliano; Mazzon, Emanuela; Ronchetti, Simona; Crisafulli, Concetta; Esposito, Emanuela; Caputi, Achille P.; Riccardi, Carlo.
In: Journal of Immunology, Vol. 177, No. 1, 01.07.2006, p. 631-641.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Proinflammatory role of glucocorticoid-induced TNF receptor-related gene in acute lung inflammation
AU - Cuzzocrea, Salvatore
AU - Nocentini, Giuseppe
AU - Di Paola, Rosanna
AU - Agostini, Massimiliano
AU - Mazzon, Emanuela
AU - Ronchetti, Simona
AU - Crisafulli, Concetta
AU - Esposito, Emanuela
AU - Caputi, Achille P.
AU - Riccardi, Carlo
PY - 2006/7/1
Y1 - 2006/7/1
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=33745293611&partnerID=8YFLogxK
M3 - Article
C2 - 16785561
AN - SCOPUS:33745293611
VL - 177
SP - 631
EP - 641
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 1
ER -