18
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

      Knockdown of neurokinin-1 receptor expression by small interfering RNA prevents the development of allergic rhinitis in rats

      research-article
      , , ,
      Inflammation Research
      Springer Basel
      Allergic rhinitis, NK-1R, siRNA, Rats

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Objective and design

          This study is aimed at exploring the role of neurokinin-1 receptor (NK-1R) in the development of allergic rhinitis (AR) in rats.

          Methods

          Sprague–Dawley rats were sensitized and challenged with ovalbumin to induce AR. The rats were treated intranasally with saline, control, or NK-1R-specific small interfering RNA (siRNA) before and during the challenge period. The numbers of sneezes and nose rubs and amount of nasal secretion in individual rats were measured. The levels of NK-1R expression in the nasal mucosal tissues after the last challenge were determined. The numbers of eosinophils in the collected nasal lavage fluid and the levels of serum interleukin (IL)-5 in individual rats were determined.

          Results

          The levels of NK-1R expression in the nasal mucosal tissues of the AR rats that had been treated with saline or control siRNA were significantly higher than those in the healthy controls and the rats treated with NK-1R-specific siRNA, demonstrating NK-1R silencing. Furthermore, knockdown of NK-1R expression significantly reduced the amounts of sneezing, nose rubbing, and nasal secretions in AR rats. Knockdown of NK-1R expression also significantly eliminated eosinophil infiltration in the nasal tissues and reduced the levels of serum IL-5 in rats.

          Conclusions

          Knockdown of NK-1R expression decreased allergic inflammation in nasal mucosal tissues and alleviated the allergic rhinitis symptoms, suggesting that NK-1R may be a critical mediator of the development of AR.

          Related collections

          Most cited references38

          • Record: found
          • Abstract: found
          • Article: not found

          RNA interference targeting Fas protects mice from fulminant hepatitis.

          RNA interference (RNAi) is a powerful tool to silence gene expression post-transcriptionally. However, its potential to treat or prevent disease remains unproven. Fas-mediated apoptosis is implicated in a broad spectrum of liver diseases, where inhibiting hepatocyte death is life-saving. We investigated the in vivo silencing effect of small interfering RNA (siRNA) duplexes targeting the gene Fas (also known as Tnfrsf6), encoding the Fas receptor, to protect mice from liver failure and fibrosis in two models of autoimmune hepatitis. Intravenous injection of Fas siRNA specifically reduced Fas mRNA levels and expression of Fas protein in mouse hepatocytes, and the effects persisted without diminution for 10 days. Hepatocytes isolated from mice treated with Fas siRNA were resistant to apoptosis when exposed to Fas-specific antibody or co-cultured with concanavalin A (ConA)-stimulated hepatic mononuclear cells. Treatment with Fas siRNA 2 days before ConA challenge abrogated hepatocyte necrosis and inflammatory infiltration and markedly reduced serum concentrations of transaminases. Administering Fas siRNA beginning one week after initiating weekly ConA injections protected mice from liver fibrosis. In a more fulminant hepatitis induced by injecting agonistic Fas-specific antibody, 82% of mice treated with siRNA that effectively silenced Fas survived for 10 days of observation, whereas all control mice died within 3 days. Silencing Fas expression with RNAi holds therapeutic promise to prevent liver injury by protecting hepatocytes from cytotoxicity.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            A survey of the burden of allergic rhinitis in Europe.

            The perceptions of patients and physicians regarding the symptoms and impact of allergic rhinitis (AR) were assessed in a prospective, cross-sectional, international survey. This paper presents the combined survey results from five European countries (Germany, France, Italy, Spain and the UK). Data were recorded by 1,482 patients and matched with records from 415 primary care physicians and specialists. Diagnostic tests to confirm AR had been performed on 1,279 (86.3%) patients. Both physicians and patients recorded the presence, severity and impact of symptoms at the time of consultation in addition to those symptoms frequently, but not currently, present. Health-related quality of life (HRQoL) was assessed using the Mini Rhinoconjunctivitis Quality of Life Questionnaire. A large proportion of patients had moderate-severe disease (67.2%; n = 996), persistent disease (42.5%; n = 630) and comorbidities such as asthma (31.5%; n = 467). Overall, patients rated their disease as more severe than did physicians (P < 0.001). At the time of the consultation, one-third of all patients reported that their current nasal and ocular symptoms were moderate or severe in nature. According to the physicians' assessment, good control of nasal and ocular symptoms was achieved in 45.4% (n = 673) and 51.3% (n = 760) of patients, respectively, and poor symptom control in 18.0% (n = 267) and 12.1% (n = 179). Overall, 43.3% (n = 641) of those surveyed were using two or more medicines for their AR. Health-related quality of life was correlated with disease severity and with the number of days without symptoms in the previous 4 weeks. Allergic rhinitis had a significantly greater impact in patients with more persistent disease than in those with intermittent disease (2.3 +/- 1.3 vs 1.9 +/- 1.2; P < 0.001). Nonetheless, 81.8% (n = 601) of patients with intermittent disease reported some impairment of their daily life as a result of their AR. Allergic rhinitis remains a significant health problem because of the high burden of symptoms and its impact on general well being and HRQoL among patients consulting for this condition. Overall, there was a poor correlation between patients and physicians in the reporting of disease severity.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Efficient delivery of siRNA for inhibition of gene expression in postnatal mice.

              It has recently been shown that RNA interference can be induced in cultured mammalian cells by delivery of short interfering RNAs (siRNAs). Here we describe a method for efficient in vivo delivery of siRNAs to organs of postnatal mice and demonstrate effective and specific inhibition of transgene expression in a variety of organs.
                Bookmark

                Author and article information

                Contributors
                +86-21-62483180 , zhang_ruxin@126.com , zhangruxin@hotmail.com
                Journal
                Inflamm Res
                Inflamm. Res
                Inflammation Research
                Springer Basel (Basel )
                1023-3830
                1420-908X
                11 August 2013
                11 August 2013
                2013
                : 62
                : 903-910
                Affiliations
                Department of Otorhinolaryngology, Huadong Hospital, Shanghai Medical College, Fudan University, Shanghai, 200040 China
                Author notes

                Responsible Editor: Michael Parnham.

                Article
                649
                10.1007/s00011-013-0649-5
                3771433
                23934070
                5c7f03be-fd3a-4378-a50c-bfb5dfeb2681
                © The Author(s) 2013

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.

                History
                : 23 March 2013
                : 24 July 2013
                Categories
                Original Research Paper
                Custom metadata
                © Springer Basel 2013

                Immunology
                allergic rhinitis,nk-1r,sirna,rats
                Immunology
                allergic rhinitis, nk-1r, sirna, rats

                Comments

                Comment on this article