title: Fluticasone furoate is more effective than mometasone furoate in restoring tobacco smoke inhibited SOCS-3 expression in airway epithelial cells.
abstract: Fluticasone furoate (FF) and mometasone furoate (MF) are potent glucocorticoids recommended for the treatment of allergic rhinitis and other inflammatory diseases. However, whether these drugs render any anti-inflammatory effects in Chronic Obstructive Pulmonary Disease (COPD) is unclear. Emerging data on suppressors of cytokine signaling-3 (SOCS-3) activation in the lungs during inflammation suggests that SOCS3 can be potential targets for regulating pulmonary inflammatory responses in COPD. In this study, we compared the effect of FF with MF on SOCS-3 expression in tobacco smoke (TS) exposed BAEpCs in vitro and in a mouse model of COPD in vivo. BAEpCs were exposed to TS or room air and later were treated with either FF (1nmol-100nmol) or MF (10-500nmol) inhibitors in the presence and absence of Jak1 and Stat-3 inhibitors. C57BL/6 mice were exposed to TS for 6 months, and treated with either FF, MF for 2 and 4 weeks. FF induced 7 fold increases in SOCS-3 expression in BAEpCs whereas MF induced a three fold increase when compared to control. Jak1 and Stat-3 inhibitors significantly inhibited the FF and MF induced SOCS-3 expression in BAEpCs. In addition, FF and MF restored TS inhibited SOCS-3 expression in the airway epithelium of COPD mice. FF and MF treatments significantly reduced leukocyte infiltration in airways and inhibited lung inflammation. Our study elucidates a novel mechanism for the anti-inflammatory action of FF in COPD. The superior efficacy of FF may be in part due to the increased expression of SOCS-3 in BAEpCs.
authors.affiliation: Division of Pulmonary Critical Care & Sleep Medicine, College of Medicine, University of Florida, United States; NF/SGVHS, Malcom Randal VA Medical Center, Gainesville, FL, United States.
authors.forename: Najmunnisa
authors.initials: N
authors.lastname: Nasreen
authors.affiliation: Division of Pulmonary Critical Care & Sleep Medicine, College of Medicine, University of Florida, United States.
authors.forename: Lixandra
authors.initials: L
authors.lastname: Gonzalves
authors.affiliation: Division of Pulmonary Critical Care & Sleep Medicine, College of Medicine, University of Florida, United States; NF/SGVHS, Malcom Randal VA Medical Center, Gainesville, FL, United States.
authors.forename: Sriram
authors.initials: S
authors.lastname: Peruvemba
authors.affiliation: Division of Pulmonary Critical Care & Sleep Medicine, College of Medicine, University of Florida, United States; NF/SGVHS, Malcom Randal VA Medical Center, Gainesville, FL, United States. Electronic address: mkamal@medicine.ufl.edu.
authors.forename: Kamal A
authors.initials: KA
authors.lastname: Mohammed
mesh_terms: D000730:Androstadienes / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001980:Bronchi / Q000166:cytology; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D005938:Glucocorticoids / Q000494:pharmacology; D006801:Humans; D053613:Janus Kinase 1 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D000068656:Mometasone Furoate; D011244:Pregnadienediols / Q000494:pharmacology*; D029424:Pulmonary Disease, Chronic Obstructive / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000037:antagonists & inhibitors / Q000235:genetics*; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*
chemical_list: D000730:Androstadienes; D000893:Anti-Inflammatory Agents; D005938:Glucocorticoids; D011244:Pregnadienediols; D012333:RNA, Messenger; C106644:SOCS3 protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C491411:Socs3 protein, mouse; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D014028:Tobacco Smoke Pollution; D000068656:Mometasone Furoate; C507904:JAK1 protein, human; D053613:Janus Kinase 1; C523187:fluticasone furoate
keywords: Bronchial airway epithelium; COPD; Fluticasone furoate; Mometasone furoate; SOCS3; Tobacco smoke