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Ribosomal protein S3 gene silencing protects against experimental allergic asthma.
Dong, Jinrui; Liao, Wupeng; Peh, Hong Yong; Chan, Tze Khee; Tan, W S Daniel; Li, Li; Yong, Amy; Wong, W S Fred.
Afiliación
  • Dong J; Department of Pharmacology, Yong Loo Lin School of Medicine, National University Health System, Singapore.
  • Liao W; Department of Pharmacology, Yong Loo Lin School of Medicine, National University Health System, Singapore.
  • Peh HY; Department of Pharmacology, Yong Loo Lin School of Medicine, National University Health System, Singapore.
  • Chan TK; Department of Pharmacology, Yong Loo Lin School of Medicine, National University Health System, Singapore.
  • Tan WS; Interdisciplinary Research Group in Infectious Diseases, Singapore-MIT Alliance for Research and Technology (SMART), Singapore.
  • Li L; Department of Pharmacology, Yong Loo Lin School of Medicine, National University Health System, Singapore.
  • Yong A; Department of Pharmacology, Yong Loo Lin School of Medicine, National University Health System, Singapore.
  • Wong WS; Department of Pharmacology and Therapeutics, Faculty of Life Sciences and Medicine, King's College London, London, UK.
Br J Pharmacol ; 174(7): 540-552, 2017 04.
Article en En | MEDLINE | ID: mdl-28093718
BACKGROUND AND PURPOSE: 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. EXPERIMENTAL APPROACH: 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). KEY RESULTS: 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. CONCLUSIONS AND IMPLICATIONS: RPS3 gene silencing ameliorates experimental asthma, probably by disrupting NF-κB activity. RPS3 could be a novel therapeutic target for allergic airway inflammation.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Asma / Proteínas Ribosómicas / Silenciador del Gen Límite: Animals Idioma: En Revista: Br J Pharmacol Año: 2017 Tipo del documento: Article País de afiliación: Singapur

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Asma / Proteínas Ribosómicas / Silenciador del Gen Límite: Animals Idioma: En Revista: Br J Pharmacol Año: 2017 Tipo del documento: Article País de afiliación: Singapur