PT  - JOURNAL ARTICLE
AU  - Arianna Carolina Rosa
AU  - Alessandro Pini
AU  - Laura Lucarini
AU  - Cecilia Lanzi
AU  - Eleonora Veglia
AU  - Robin L Thurmond
AU  - Holger Stark
AU  - Emanuela Masini
TI  - Prevention of Bleomycin-Induced Lung Inflammation and Fibrosis in Mice by Naproxen and JNJ7777120 Treatment
AID  - 10.1124/jpet.114.215152
DP  - 2014 Jan 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - jpet.114.215152
4099  - http://jpet.aspetjournals.org/content/early/2014/09/02/jpet.114.215152.short
4100  - http://jpet.aspetjournals.org/content/early/2014/09/02/jpet.114.215152.full
AB  - Pulmonary fibrosis, a progressive and lethal lung disease characterized by inflammation and accumulation of extracellular matrix components, is one of major therapeutic challenge, where new therapeutic strategies are warranted. COX inhibitors have been previously utilized to reduce inflammation. Histamine H4 receptor (H4R), largely expressed in haematopoietic cells, has been identified as a novel target for inflammatory and immune disorders. The aim of this study was to evaluate the effect of JNJ7777120, a selective H4R antagonist, and naproxen, a well-known NSAID, and their combination in a murine model of bleomycin-induced fibrosis. Bleomycin (0.05 IU) was instilled intra-tracheally to C57BL/6 mice, which were then treated by micro-osmotic pump with vehicle, JNJ7777120 (40 mg/kg/b.wt.), naproxen (21 mg/kg/b.wt.) or a combination of both. Airway resistance to inflation, an index of lung stiffness, was assessed and lung specimens were processed for inflammation, oxidative stress and fibrosis markers. Both the drugs alone were able to reduce the airway resistance to inflation induced by bleomycin and the inflammatory response by decreasing the COX-2 and MPO expression and activity and TBARS and 8-OHdG production. Lung fibrosis was inhibited as demonstrated by the reduction of tissue levels of TGF-β, collagen deposition, relative goblet cell number and smooth muscle layer thickness. Our results demonstrate that both JNJ7777120 and naproxen exert an anti-inflammatory and anti-fibrotic effect increased by their combination, which could be an effective therapeutic strategy in the treatment of pulmonary fibrosis.