PT - JOURNAL ARTICLE AU - Jinrui Dong AU - Wupeng Liao AU - Hong Yong Peh AU - Tze Khee Chan AU - W.S. Daniel Tan AU - Li Li AU - W.S. Fred Wong TI - Ribosomal protein S3 gene silencing protects against experimental allergic asthma AID - 10.1183/13993003.congress-2016.PA562 DP - 2016 Sep 01 TA - European Respiratory Journal PG - PA562 VI - 48 IP - suppl 60 4099 - http://erj.ersjournals.com/content/48/suppl_60/PA562.short 4100 - http://erj.ersjournals.com/content/48/suppl_60/PA562.full SO - Eur Respir J2016 Sep 01; 48 AB - Ribosomal protein S3 (RPS3) is a 40S ribosomal protein from the S3P family essential for executing 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 RPS3 gene silencing via small interfering RNA (siRNA) can ameliorate allergic airway inflammation. A 21-mer siRNA potently knocked down RPS3 level confirmed in both RAW 264.7 and NIH/3T3 cell lines, and markedly reduced TNF-α-induced pro-inflammatory cytokine production by the cells. In a HDM mouse asthma model, RPS3 protein level in the lungs was found for the first time to be up-regulated, and intratracheal RPS3 siRNA drastically knocked down lung RPS3 level and reduced total and eosinophil counts, as well as IL-1β, IL-4, IL-5, IL-8, IL-13 and eotaxin levels in the bronchoalveolar lavage fluid. RPS3 gene silencing evidently abated HDM-induced airway mucus hypersecretion, pro-inflammatory mediator gene expression in lung tissues, and serum IgE and HDM-specific IgE levels. Moreover, pulmonary RPS3 knockdown significantly suppressed methacholine-induced airway hyperresponsiveness. Mechanistically, RPS3 siRNA not only disrupted TNF-α-induced NF-κB activation illustrated in a NF-κB reporter gene assay in vitro, but also mitigated nuclear accumulation of p65 subunit and p65 transcriptional activation in HDM-challenged lungs. We reported here for the first time that RPS3 gene silencing ameliorates experimental allergic asthma, probably via interruption of NF-κB activity, confirming RPS3 a novel therapeutic target for the treatment of allergic airway inflammation.