title: Parabromophenacyl bromide inhibits subepithelial fibrosis by reducing TGF-β1 in a chronic mouse model of allergic asthma.
abstract: BACKGROUND
  Our previous study showed that parabromophenacyl bromide (PBPB) inhibits the features of allergic airway inflammation and airway hyperresponsiveness (AHR). However, its effect on airway remodeling, e.g. subepithelial ﬁbrosis in a chronic allergic asthma model, was not investigated. We examined this issue in this study.
  
  
  METHODS
  PBPB was administered to mice with an induced chronic asthmatic condition. AHR was estimated at the end of the experiment, followed by euthanasia. Lung sections were stained with hematoxylin and eosin, periodic acid-Schiff and Masson's trichrome to determine airway inflammation, goblet cell metaplasia and subepithelial fibrosis, respectively. Transforming growth factor-β1 (TGF-β1) was estimated in lung homogenates. To determine the effect of PBPB on smooth-muscle hyperplasia, immunohistochemistry against α-smooth-muscle actin was performed on the lung sections.
  
  
  RESULTS
  Chronic ovalbumin challenges in a mouse model of allergic asthma caused significant subepithelial ﬁbrosis and elevated TGF-β1, along with significant AHR. PBPB attenuated subepithelial ﬁbrosis with a reduction of lung TGF-β1, airway inflammation and AHR without affecting goblet cell metaplasia. It also attenuated smooth-muscle hyperplasia with a reduction in the expression of α-smooth-muscle actin in the lungs.
  
  
  CONCLUSIONS
  Our findings indicate that PBPB attenuates some crucial features of airway remodeling such as subepithelial ﬁbrosis and smooth-muscle hyperplasia. These data suggest that PBPB could therefore be a therapeutic drug for chronic asthma.
authors: CSIR Institute of Genomics and Integrative Biology, Delhi, India.
authors: Arjun
authors: A
authors: Ram
authors: Ulaganathan
authors: U
authors: Mabalirajan
authors: Ashish
authors: A
authors: Jaiswal
authors: Rakhshinda
authors: R
authors: Rehman
authors: Vijay Pal
authors: VP
authors: Singh
authors: Balaram
authors: B
authors: Ghosh
mesh_terms: D000098:Acetophenones / Q000494:pharmacology*; D000199:Actins / Q000378:metabolism; D056151:Airway Remodeling / Q000187:drug effects; D000818:Animals; D001249:Asthma / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D005355:Fibrosis; D020397:Goblet Cells / Q000187:drug effects / Q000473:pathology; D008168:Lung / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008679:Metaplasia; D051379:Mice; D008807:Mice, Inbred BALB C; D064801:Phospholipase A2 Inhibitors / Q000494:pharmacology; D012130:Respiratory Hypersensitivity / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D015398:Signal Transduction / Q000187:drug effects; D053773:Transforming Growth Factor beta1 / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000098:Acetophenones; D000199:Actins; D064801:Phospholipase A2 Inhibitors; D053773:Transforming Growth Factor beta1; C544013:alpha-smooth muscle actin, mouse; C006821:4-bromophenacyl bromide