Inhibition or knock out of Inducible nitric oxide synthase result in resistance to bleomycin-induced lung injury |
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Authors: | Tiziana Genovese Salvatore Cuzzocrea Rosanna Di Paola Marco Failla Emanuela Mazzon Maria Angela Sortino Giuseppina Frasca Elisa Gili Nunzio Crimi Achille P Caputi Carlo Vancheri |
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Affiliation: | 1.Department of Clinical and Experimental Medicine and Pharmacology, Torre Biologica, Policlinico Universitario, 98123 Messina, Italy;2.Department of Internal and Specialistic Medicine, Section of Respiratory Diseases, University of Catania, Catania, Italy;3.Department of Experimental and Clinical Pharmacology, University of Catania, Catania, Italy |
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Abstract: | BackgroundIn the present study, by comparing the responses in wild-type mice (WT) and mice lacking (KO) the inducible (or type 2) nitric oxide synthase (iNOS), we investigated the role played by iNOS in the development of on the lung injury caused by bleomycin administration. When compared to bleomycin-treated iNOSWT mice, iNOSKO mice, which had received bleomycin, exhibited a reduced degree of the (i) lost of body weight, (ii) mortality rate, (iii) infiltration of the lung with polymorphonuclear neutrophils (MPO activity), (iv) edema formation, (v) histological evidence of lung injury, (vi) lung collagen deposition and (vii) lung Transforming Growth Factor beta1 (TGF-β1) expression.MethodsMice subjected to intratracheal administration of bleomycin developed a significant lung injury. Immunohistochemical analysis for nitrotyrosine revealed a positive staining in lungs from bleomycin-treated iNOSWT mice.ResultsThe intensity and degree of nitrotyrosine staining was markedly reduced in tissue section from bleomycin-iNOSKO mice. Treatment of iNOSWT mice with of {"type":"entrez-nucleotide","attrs":{"text":"GW274150","term_id":"282552565","term_text":"GW274150"}}GW274150, a novel, potent and selective inhibitor of iNOS activity (5 mg/kg i.p.) also significantly attenuated all of the above indicators of lung damage and inflammation.ConclusionTaken together, our results clearly demonstrate that iNOS plays an important role in the lung injury induced by bleomycin in the mice. |
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