Ribosomal protein S3 gene silencing protects against experimental allergic asthma
Jinrui Dong (Singapore, Singapore), Jinrui Dong, Wupeng Liao, Hong Yong Peh, Tze Khee Chan, W.S. Daniel Tan, Li Li, W.S. Fred Wong
Source: International Congress 2016 – Asthma: mechanisms and biomarkers that promote clinical understanding
Disease area: Airway diseases
Abstract 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-k B complex, and promote p65 DNA-binding activity. Persistent activation of the NF-k B 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-a -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-1b , 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-a -induced NF-k B activation illustrated in a NF-k B 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-k B activity, confirming RPS3 a novel therapeutic target for the treatment of allergic airway inflammation.
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Jinrui Dong (Singapore, Singapore), Jinrui Dong, Wupeng Liao, Hong Yong Peh, Tze Khee Chan, W.S. Daniel Tan, Li Li, W.S. Fred Wong. Ribosomal protein S3 gene silencing protects against experimental allergic asthma. Eur Respir J 2016; 48: Suppl. 60, 562
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