title: Ribosomal protein S3 gene silencing protects against experimental allergic asthma.
abstract: Ribosomal protein S3 (RPS3) is a 40S ribosomal protein of the S3P family essential for implementing protein translation. RPS3 has recently been found to interact with the p65 subunit of the NF-κB complex and promote p65 DNA-binding activity. Persistent activation of the NF-κB pathway is evident in allergic asthma. We hypothesized that gene silencing of lung RPS3 can ameliorate allergic airway inflammation.
  
  
  
  The gene silencing efficacy of RPS3 siRNA was screened in three different mouse cell lines by real-time PCR and immunoblotting. Protective effects of intratracheal RPS3 siRNA in a house dust mite (HDM) mouse asthma model were determined by measuring cell counts in lung lavage fluid and lung sections, lung cytokine profiles and airway hyperresponsiveness (AHR).
  
  
  
  RPS3 siRNA markedly knocked down RPS3 levels in all mouse cell lines tested, and in mouse lung tissues, blocked TNF-α- or HDM-induced release of mediators by the cultured cells and reduced eosinophil counts in lung lavage fluid from the HDM mouse asthma model. RPS3 siRNA lessened HDM-induced airway mucus hypersecretion, cytokine production and serum IgE elevation. Moreover, RPS3 knockdown significantly suppressed methacholine-induced AHR in experimental asthma. RPS3 siRNA disrupted TNF-α-induced NF-κB activation in a NF-κB reporter gene assay in vitro and prevented the nuclear accumulation of p65 subunit and p65 transcriptional activation in HDM-challenged lungs and cells.
  
  
  
  RPS3 gene silencing ameliorates experimental asthma, probably by disrupting NF-κB activity. RPS3 could be a novel therapeutic target for allergic airway inflammation.
authors.affiliation: Department of Pharmacology, Yong Loo Lin School of Medicine, National University Health System, Singapore.
authors.forename: Jinrui
authors.initials: J
authors.lastname: Dong
authors.affiliation: Department of Pharmacology, Yong Loo Lin School of Medicine, National University Health System, Singapore.
authors.forename: Wupeng
authors.initials: W
authors.lastname: Liao
authors.affiliation: Department of Pharmacology, Yong Loo Lin School of Medicine, National University Health System, Singapore.
authors.forename: Hong Yong
authors.initials: HY
authors.lastname: Peh
authors.affiliation: Department of Pharmacology, Yong Loo Lin School of Medicine, National University Health System, Singapore.|Interdisciplinary Research Group in Infectious Diseases, Singapore-MIT Alliance for Research and Technology (SMART), Singapore.
authors.forename: Tze Khee
authors.initials: TK
authors.lastname: Chan
authors.affiliation: Department of Pharmacology, Yong Loo Lin School of Medicine, National University Health System, Singapore.
authors.forename: W S Daniel
authors.initials: WS
authors.lastname: Tan
authors.affiliation: Department of Pharmacology, Yong Loo Lin School of Medicine, National University Health System, Singapore.
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Pharmacology and Therapeutics, Faculty of Life Sciences and Medicine, King's College London, London, UK.
authors.forename: Amy
authors.initials: A
authors.lastname: Yong
authors.affiliation: Department of Pharmacology, Yong Loo Lin School of Medicine, National University Health System, Singapore.|Immunology Program, Life Science Institute, National University of Singapore, Singapore.
authors.forename: W S Fred
authors.initials: WS
authors.lastname: Wong
mesh_terms: D000818:Animals; D001249:Asthma / Q000235:genetics* / Q000517:prevention & control* / Q000628:therapy; D005260:Female; D020868:Gene Silencing; D015316:Genetic Therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D041681:NIH 3T3 Cells; D000067996:RAW 264.7 Cells; D012269:Ribosomal Proteins / Q000235:genetics*
chemical_list: D012269:Ribosomal Proteins; C044152:ribosomal protein S3