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Cuzzocrea, S. et al.

Cuzzocrea, Ronchetti, Genovese, Mazzon, Agostini, Di Paola, Esposito, Mui??, Nocentini, Riccardi,

Genetic and pharmacological inhibition of GITR-GITRL interaction reduces chronic lung injury induced by bleomycin instillation.

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, dendritic 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-alpha and interleukin (IL)-1beta production; v) nitrotyrosine formation; and vi) NF-kappaB activation. The cotreatment of GITR+/+ mice with Fc-GITR fusion protein (6.25 microg/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.[1]

References

Genetic and pharmacological inhibition of GITR-GITRL interaction reduces chronic lung injury induced by bleomycin instillation. Cuzzocrea, S., Ronchetti, S., Genovese, T., Mazzon, E., Agostini, M., Di Paola, R., Esposito, E., Mui??, C., Nocentini, G., Riccardi, C. FASEB J. (2007) [Pubmed]

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