23
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      The Effects of Nebulized Inhaled Triptolide on Airway Inflammation in a Mouse Model of Asthma

      research-article
      , , , ,
      Canadian Respiratory Journal
      Hindawi

      Read this article at

      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

          Inhalation of nebulized TP has received little attention in the past. Here, we intend to investigate the effect of nebulized inhaled TP on airway inflammation in a mouse model of asthma. 29 SPF BALB/c mice were divided into four groups: blank control (Blk, n = 5), normal saline (NS, n = 8), dexamethasone (Dex, n = 8), and TP ( n = 8). During the process of sensitization, mice in the three intervention groups were treated with nebulized NS, an injection of Dex, and nebulized triptolide, respectively. Then bronchoalveolar lavage fluid (BALF), peripheral blood, and lung tissue were collected. Relevant cytokines, transcriptional factors, and CD4+Th17+ T cell proportions were assessed and compared. IL-6, IL-17, IL-23, and TGF- β1 demonstrated a significant difference between groups in the following order: Dex < TP < NS ( P ≤ 0.001), while IL-10 changed in the opposite direction ( P < 0.001). At the transcriptional level in lung tissue, the Ct value of IL-17 in the Dex group was significantly higher than in the NS and TP groups ( P < 0.001). Meanwhile, it was higher in the TP group than in the NS group ( P < 0.001). The Ct value of ROR γt demonstrated a significant difference among three groups in the following order: Dex > TP > NS ( P < 0.001). An opposite trend of FoxP3 Ct value was revealed in the order: NS > TP > Dex. The proportion of CD4+Th17+ cells was 9.53 ± 2.74% in the NS group, 4.23 ± 2.26% in the Dex group, and 6.76 ± 2.99% in the TP group, which shows significant differences between the NS and Dex ( P < 0.001) or NS and TP groups ( P < 0.05). Inhalation of nebulized triptolide can play a role in suppressing airway inflammation with inflammatory cytokines and transcriptional factors reduced and CD4+Th17+ T cells dampened, also in a manner less than injected dexamethasone.

          Related collections

          Most cited references21

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

          XPB, a subunit of TFIIH, is a target of the natural product triptolide.

          Triptolide (1) is a structurally unique diterpene triepoxide isolated from a traditional Chinese medicinal plant with anti-inflammatory, immunosuppressive, contraceptive and antitumor activities. Its molecular mechanism of action, however, has remained largely elusive to date. We report that triptolide covalently binds to human XPB (also known as ERCC3), a subunit of the transcription factor TFIIH, and inhibits its DNA-dependent ATPase activity, which leads to the inhibition of RNA polymerase II-mediated transcription and likely nucleotide excision repair. The identification of XPB as the target of triptolide accounts for the majority of the known biological activities of triptolide. These findings also suggest that triptolide can serve as a new molecular probe for studying transcription and, potentially, as a new type of anticancer agent through inhibition of the ATPase activity of XPB.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Neutrophil cytoplasts induce TH17 differentiation and skew inflammation toward neutrophilia in severe asthma

            Severe asthma is a debilitating and treatment refractory disease. As many as half of these patients have complex neutrophil-predominant lung inflammation that is distinct from milder asthma with type 2 eosinophilic inflammation. New insights into severe asthma pathogenesis are needed. Concomitant exposure of mice to an aeroallergen and endotoxin during sensitization resulted in complex neutrophilic immune responses to allergen alone during later airway challenge. Unlike allergen alone, sensitization with allergen and endotoxin led to NETosis. In addition to neutrophil extracellular traps (NETs), enucleated neutrophil cytoplasts were evident in the lungs. Surprisingly, allergen-driven airway neutrophilia was decreased in peptidyl arginine deiminase 4–deficient mice with defective NETosis but not by deoxyribonuclease treatment, implicating the cytoplasts for the non–type 2 immune responses to allergen. Neutrophil cytoplasts were also present in mediastinal lymph nodes, and the cytoplasts activated lung dendritic cells in vitro to trigger antigen-specific interleukin-17 (IL-17) production from naïve CD4+ T cells. Bronchoalveolar lavage fluid from patients with severe asthma and high neutrophil counts had detectable NETs and cytoplasts that were positively correlated with IL-17 levels. Together, these translational findings have identified neutrophil cytoplast formation in asthmatic lung inflammation and linked the cytoplasts to T helper 17–mediated neutrophilic inflammation in severe asthma.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: found
              Is Open Access

              Application and Mechanisms of Triptolide in the Treatment of Inflammatory Diseases—A Review

              Bioactive compounds from medicinal plants with anti-inflammatory and immunosuppressive effects have been emerging as important sources of drugs for the treatment of inflammatory disorders. Triptolide, a diterpene triepoxide, is a pharmacologically active compound isolated from Tripterygium wilfordii Hook F (TwHF) that is used as a remedy for inflammatory and autoimmune diseases. As the most promising bioactive compound obtained from TwHF, triptolide has attracted considerable interest recently, especially for its potent anti-inflammatory and immunosuppressive activities. Over the past few years, an increasing number of studies have been published emphasizing the value of triptolide in the treatment of diverse inflammatory disorders. Here, we systematically review the mechanism of action and the therapeutic properties of triptolide in various inflammatory diseases according to different systematic organs, including lupus nephritis, inflammatory bowel disease, asthma, and rheumatoid arthritis with pubmed and Embase. Based on this review, potential research strategies might contribute to the clinical application of triptolide in the future.
                Bookmark

                Author and article information

                Contributors
                Journal
                Can Respir J
                Can Respir J
                CRJ
                Canadian Respiratory Journal
                Hindawi
                1198-2241
                1916-7245
                2023
                21 August 2023
                : 2023
                : 2983092
                Affiliations
                PCCM, Shanghai University of Medicine & Health Sciences Affiliated Zhoupu Hospital, Shanghai 201318, China
                Author notes

                Academic Editor: Sami Deniz

                Author information
                https://orcid.org/0000-0003-0468-9012
                Article
                10.1155/2023/2983092
                10462443
                37645252
                3a604bb7-b4bb-4cd3-a667-3e316ca9e6fb
                Copyright © 2023 Yafang Miao et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 14 November 2022
                : 31 March 2023
                : 27 July 2023
                Funding
                Funded by: Shanghai University of Medicine and Health Sciences
                Award ID: ZPBRK-18-08
                Award ID: HMSF-17-22-038
                Funded by: Shanghai Municipal Health and Family Planning Commission
                Award ID: 201740310
                Funded by: Shanghai Pudong New Area Health Commission
                Award ID: PWZxk2017–22
                Categories
                Research Article

                Comments

                Comment on this article