Pulmonary fibrosis is a progressive and lethal lung disease characterized by lung inflammation and abnormal remod- eling of lung parenchyma. At the moment no cure exists for this disease. The histamine H4R, widely expressed on cell of immune origin, plays an important role in inflammatory processes. We previously demonstrated that JNJ7777120 (JNJ), a H4R antagonist, decreases the inflammatory response in animal models of asthma and carrageenan- induced pleurisy. The aim of this study was to investigate the anti- inflammatory and anti-fibrotic effects of the histamine H4R antagonist JNJ in a mouse model of bleomycin-induced pulmonary fibrosis. We also compared the effects of JNJ with those of naproxen, a classical NSAID. The bleomycin- induced mice were treated with vehicle or JNJ (total dose 40 mg/kg bw) or equimolar naproxen, released by micro- osmotic pumps. Airway resistance to inflation, an index of lung stiffness, was assayed and lung tissue was processed to evaluate inflammation and fibrosis biochemically and histologically. JNJ exerted an anti-inflammatory effect, as shown by a significant decrease in the levels of PGE2, myeloperoxi- dase, an index of leukocyte infiltration, and thiobarbituric acid reactive substances, markers of oxidative stress. JNJ administration also reduced the relative number of goblet cells and the thickness of smooth muscle layer, two key parameters of inflammation-induced adverse bronchial remodeling. Moreover, treatment with JNJ resulted in a strong inhibition of lung fibrosis, as shown by the reduction of the tissue levels of the pro-fibrotic cytokine TGF-b and of collagen; this was accompanied by a decrease in airway resistance to inflation. No significant differences were observed between the JNJ and naproxen treatment. Our results indicated that JNJ exerted an anti- inflammatory and anti-fibrotic activity and may offer a new therapeutic option for the treatment of pulmonary fibrosis.

Prevention of bleomycin-induced pulmonary fibrosis by a selective histamine H(4)R antagonist / Pini A; Somma T; Formicola G; Thurmond RT; Bani D; Masini E.. - In: INFLAMMATION RESEARCH. - ISSN 1023-3830. - STAMPA. - (2011), pp. S 335-S 335.

Prevention of bleomycin-induced pulmonary fibrosis by a selective histamine H(4)R antagonist.

PINI, ALESSANDRO;BANI, DANIELE;MASINI, EMANUELA
2011

Abstract

Pulmonary fibrosis is a progressive and lethal lung disease characterized by lung inflammation and abnormal remod- eling of lung parenchyma. At the moment no cure exists for this disease. The histamine H4R, widely expressed on cell of immune origin, plays an important role in inflammatory processes. We previously demonstrated that JNJ7777120 (JNJ), a H4R antagonist, decreases the inflammatory response in animal models of asthma and carrageenan- induced pleurisy. The aim of this study was to investigate the anti- inflammatory and anti-fibrotic effects of the histamine H4R antagonist JNJ in a mouse model of bleomycin-induced pulmonary fibrosis. We also compared the effects of JNJ with those of naproxen, a classical NSAID. The bleomycin- induced mice were treated with vehicle or JNJ (total dose 40 mg/kg bw) or equimolar naproxen, released by micro- osmotic pumps. Airway resistance to inflation, an index of lung stiffness, was assayed and lung tissue was processed to evaluate inflammation and fibrosis biochemically and histologically. JNJ exerted an anti-inflammatory effect, as shown by a significant decrease in the levels of PGE2, myeloperoxi- dase, an index of leukocyte infiltration, and thiobarbituric acid reactive substances, markers of oxidative stress. JNJ administration also reduced the relative number of goblet cells and the thickness of smooth muscle layer, two key parameters of inflammation-induced adverse bronchial remodeling. Moreover, treatment with JNJ resulted in a strong inhibition of lung fibrosis, as shown by the reduction of the tissue levels of the pro-fibrotic cytokine TGF-b and of collagen; this was accompanied by a decrease in airway resistance to inflation. No significant differences were observed between the JNJ and naproxen treatment. Our results indicated that JNJ exerted an anti- inflammatory and anti-fibrotic activity and may offer a new therapeutic option for the treatment of pulmonary fibrosis.
2011
Pini A; Somma T; Formicola G; Thurmond RT; Bani D; Masini E.
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/958148
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