|
|
||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
E-mail contact: salvator@unime.it
We have recently identified a gene named GITR (glucocorticoid-induced TNF receptor related gene). GITR is expressed in different cells and tissues such as T lymphocytes from thymus and spleen and lymph nodes, and also in the lung. GITR ligand (GITRL) is expressed in several cells including macrophages, B cells, denditric cells, and endothelial cells. In the present study, by comparing the responses in wild-type (WT) mice (GITR+/+) and GITR-deficient mice (GITR-/-), we investigated the role played by GITR-GITRL interaction in the development of chronic lung injury caused by bleomycin instillation. When compared with bleomycin-treated GITR+/+ mice, bleomycin-treated GITR-/- mice exhibited a reduced degree of i) lung infiltration with polymorphonuclear neutrophils (MPO activity); ii) edema formation; iii) histological evidence of lung injury; iv) TNF-
and interleukin (IL)-1
production; v) nitrotyrosine formation; and iv) NF-
B activation. The cotreatment of GITR+/+ mice with Fc-GITR fusion protein (6.25 µg/mouse) also significantly attenuated all of the above indicators of lung damage and inflammation. Our results clearly demonstrate that GITR-GITRL interaction plays an important role in the chronic lung injury induced by bleomycin in the mice.--Cuzzocrea, S., Ronchetti, S., Genovese, T., Mazzon, E., Agostini, M., Di Paola, R., Esposito, E., Muià, C., Nocentini, G., Riccardi, C. Genetic and pharmacological inhibition of GITR-GITRL interaction reduces chronic lung injury induced by bleomycin instillation.
This article has been cited by other articles:
![]() |
Y. Kamimura, H. Iwai, J. Piao, M. Hashiguchi, and M. Azuma The Glucocorticoid-Induced TNF Receptor-Related Protein (GITR)-GITR Ligand Pathway Acts As a Mediator of Cutaneous Dendritic Cell Migration and Promotes T Cell-Mediated Acquired Immunity J. Immunol., March 1, 2009; 182(5): 2708 - 2716. [Abstract] [Full Text] [PDF] |
||||
![]() |
A.-M. Pulichino, I-M. Wang, A. Caron, J. Mortimer, A. Auger, Y. Boie, J. A. Elias, A. Kartono, L. Xu, J. Menetski, et al. Identification of Transforming Growth Factor {beta}1-Driven Genetic Programs of Acute Lung Fibrosis Am. J. Respir. Cell Mol. Biol., September 1, 2008; 39(3): 324 - 336. [Abstract] [Full Text] [PDF] |
||||
![]() |
G. Nocentini, S. Cuzzocrea, T. Genovese, R. Bianchini, E. Mazzon, S. Ronchetti, E. Esposito, D. P. Rosanna, P. Bramanti, and C. Riccardi Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related (GITR)-Fc Fusion Protein Inhibits GITR Triggering and Protects from the Inflammatory Response after Spinal Cord Injury Mol. Pharmacol., June 1, 2008; 73(6): 1610 - 1621. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Ronchetti, G. Nocentini, R. Bianchini, L. T. Krausz, G. Migliorati, and C. Riccardi Glucocorticoid-Induced TNFR-Related Protein Lowers the Threshold of CD28 Costimulation in CD8+ T Cells J. Immunol., November 1, 2007; 179(9): 5916 - 5926. [Abstract] [Full Text] [PDF] |
||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |