title: S-adenosylmethionine reduces airway inflammation and fibrosis in a murine model of chronic severe asthma via suppression of oxidative stress.
abstract: Increased oxidative stress has an important role in asthmatic airway inflammation and remodeling. A potent methyl donor, S-adenosylmethionine (SAMe), is known to protect against tissue injury and fibrosis through modulation of oxidative stress. The aim of this study was to evaluate the effect of SAMe on airway inflammation and remodeling in a murine model of chronic asthma. A mouse model was generated by repeated intranasal challenge with ovalbumin and Aspergillus fungal protease twice a week for 8 weeks. SAMe was orally administered every 24 h for 8 weeks. We performed bronchoalveolar lavage (BAL) fluid analysis and histopathological examination. The levels of various cytokines and 4-hydroxy-2-nonenal (HNE) were measured in the lung tissue. Cultured macrophages and fibroblasts were employed to evaluate the underlying anti-inflammatory and antifibrotic mechanisms of SAMe. The magnitude of airway inflammation and fibrosis, as well as the total BAL cell counts, were significantly suppressed in the SAMe-treated groups. A reduction in T helper type 2 pro-inflammatory cytokines and HNE levels was observed in mouse lung tissue after SAMe administration. Macrophages cultured with SAMe also showed reduced cellular oxidative stress and pro-inflammatory cytokine production. Moreover, SAMe treatment attenuated transforming growth factor-β (TGF-β)-induced fibronectin expression in cultured fibroblasts. SAMe had a suppressive effect on airway inflammation and fibrosis in a mouse model of chronic asthma, at least partially through the attenuation of oxidative stress and TGF-β-induced fibronectin expression. The results of this study suggest a potential role for SAMe as a novel therapeutic agent in chronic asthma.
authors.affiliation: Division of Allergy and Clinical Immunology, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.|Division of Allergy and Pulmonology, Department of Internal Medicine, Konkuk University Chungju Hospital, Chungju, Korea.
authors.forename: Sun-Young
authors.initials: SY
authors.lastname: Yoon
authors.affiliation: Asan Institute for Life Science, Seoul, Korea.
authors.forename: Gyong Hwa
authors.initials: GH
authors.lastname: Hong
authors.affiliation: Division of Allergy and Clinical Immunology, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Hyouk-Soo
authors.initials: HS
authors.lastname: Kwon
authors.affiliation: Asan Institute for Life Science, Seoul, Korea.
authors.forename: Sunjoo
authors.initials: S
authors.lastname: Park
authors.affiliation: Division of Allergy and Clinical Immunology, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: So Young
authors.initials: SY
authors.lastname: Park
authors.affiliation: Division of Allergy and Clinical Immunology, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Bomi
authors.initials: B
authors.lastname: Shin
authors.affiliation: Division of Allergy and Clinical Immunology, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Tae-Bum
authors.initials: TB
authors.lastname: Kim
authors.affiliation: Division of Allergy and Clinical Immunology, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Hee-Bom
authors.initials: HB
authors.lastname: Moon
authors.affiliation: Division of Allergy and Clinical Immunology, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: You Sook
authors.initials: YS
authors.lastname: Cho
mesh_terms: D056151:Airway Remodeling / Q000187:drug effects*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D000975:Antioxidants / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D002908:Chronic Disease; D004195:Disease Models, Animal; D005260:Female; D005355:Fibrosis; D007249:Inflammation / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D018384:Oxidative Stress / Q000187:drug effects*; D012436:S-Adenosylmethionine / Q000627:therapeutic use*
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D012436:S-Adenosylmethionine