Dataset Information

Superoxide dismutase 3 controls adaptive immune responses and contributes to the inhibition of ovalbumin-induced allergic airway inflammation in mice.

ABSTRACT: AIMS: The extracellular superoxide dismutase 3 (SOD3) is an isoform of SOD. Extensive studies have been focused on role of SOD3 as an antioxidant. However, the role of SOD3 in the immune responses that contribute to the inhibition of allergic lung inflammation has not been investigated. RESULTS: Here, we report for the first time that SOD3 specifically inhibits dendritic cell maturation. Subsequently, SOD3 controls T cell activation and proliferation, and T helper 2 (Th2) and Th17 cell differentiation. As a consequence, the administration of SOD3 into mice alleviated Th2-cell-mediated ovalbumin (OVA)-induced allergic asthma. In addition, we demonstrated that SOD3 inhibits OVA-induced airway extracellular remodeling and Th2 cell trafficking. Through mass spectrometry analysis, the proteins interacting with SOD3 in the lung of asthma were identified. And it was revealed that signaling molecules, such as transforming growth factor (TGF) and epidermal growth factor (EGF) receptor, adhesion and adaptor molecules, kinases, phosphatases, NADPH oxidase, and apoptosis-related factor, were involved, which were altered by administration of SOD3. Relatively severe asthma was observed in SOD3 KO mice and was ameliorated by both the administration of SOD3 and adoptive transfer of SOD3-sufficient CD4 T cells. Moreover, the expression of endogenous SOD3 in the lung peaked early in OVA challenge and gradually decreased upon disease progression, while both SOD1 and SOD2 expression changed relatively little. INNOVATION AND CONCLUSION: Thus, our data suggest that SOD3 is required to maintain lung homeostasis and acts, at least in part, as a controller of signaling and a decision maker to determine the progression of allergic lung disease.

SUBMITTER: Kwon MJ

PROVIDER: S-EPMC3437046 | biostudies-literature | 2012 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Superoxide dismutase 3 controls adaptive immune responses and contributes to the inhibition of ovalbumin-induced allergic airway inflammation in mice.

Kwon Myung-Ja MJ Jeon Yun-Jae YJ Lee Kyo-Young KY Kim Tae-Yoon TY

Antioxidants & redox signaling 20120629 10

<h4>Aims</h4>The extracellular superoxide dismutase 3 (SOD3) is an isoform of SOD. Extensive studies have been focused on role of SOD3 as an antioxidant. However, the role of SOD3 in the immune responses that contribute to the inhibition of allergic lung inflammation has not been investigated.<h4>Results</h4>Here, we report for the first time that SOD3 specifically inhibits dendritic cell maturation. Subsequently, SOD3 controls T cell activation and proliferation, and T helper 2 (Th2) and Th17 c ...[more]

PMID: 22583151

Similar Datasets

Project description:IntroductionExcretory/secretory products (ESPs) derived from helminths have been reported to effectively control allergic inflammation, which have better therapeutic prospects than live parasite infections. However, it remains unknown whether ESPs from schistosome eggs can protect against allergies, despite reports alleging that schistosome infection could alleviate disordered allergic inflammation.MethodIn the present study, we investigated the protective effects of ESPs from Schistosoma japonicum eggs (ESP-SJE) on asthmatic inflammation. Firstly, we successfully established an allergic airway inflammation model in mice by alum-adjuvanted ovalbumin (OVA) sensitization and challenge. ESP-SJE were administered intraperitoneally on days -1 and 13 (before sensitization), on day 20 (before challenge), and on days 21-24 (challenge phase).ResultsThe results showed that ESP-SJE treatment significantly reduced the infiltration of inflammatory cells, especially eosinophils into the lung tissue, inhibited the production of the total and OVA-specific IgE during OVA-sensitized and -challenged phases, respectively, and suppressed the secretion of Th2-type inflammatory cytokines (IL-4). Additionally, ESP-SJE treatment significantly upregulated the regulatory T cells (Tregs) in the lung tissue during OVA challenge. Furthermore, using liquid chromatography-mass spectrometry analysis and Treg induction experiments in vitro, we might identify nine potential therapeutic proteins against allergic inflammation in ESP-SJE. The targets of these candidate proteins included glutathione S-transferase, egg protein CP422 precursor, tubulin alpha-2/alpha-4 chain, actin-2, T-complex protein 1 subunit beta, histone H₄, whey acidic protein core region, and molecular chaperone HtpG.ConclusionTaken together, the results discussed herein demonstrated that ESP-SJE could significantly alleviate OVA-induced asthmatic inflammation in a murine model, which might be mediated by the upregulation of Treg in lung tissues that may be induced by the potential modulatory proteins. Therefore, potential proteins in ESP-SJE might be the best candidates to be tested for therapeutic application of asthma, thus pointing out to a possible new therapy for allergic airway inflammation.

Project description:BackgroundRecently, academic studies suggest that global growth of airway allergic disease has a close association with dietary changes including reduced consumption of fiber. Therefore, appropriate dietary fiber supplementation might be potential to prevent airway allergic disease (AAD).ObjectiveWe investigated whether dietary fiber intake suppressed the induction of AAD and tried to elucidate the possible underlying mechanisms.MethodsThe control mice and AAD model mice fed with 4% standard-fiber chow, while low-fiber group of mice fed with a 1.75% low-fiber chow. The two fiber-intervened groups including mice, apart from a standard-fiber diet, were also intragastric (i.g.) administrated daily with poorly fermentable cellulose or readily fermentable pectin (0.4% of daily body weight), respectively. All animals except normal mice were sensitized and challenged with ovalbumin (OVA) to induce airway allergic inflammation. Hallmarks of AAD were examined by histological analysis and ELISA. The variation in intestinal bacterial composition was assessed by qualitative analysis of 16S ribosomal DNA (rDNA) content in fecal samples using real-time PCR.ResultsLow-fiber diet aggravated inflammatory response in ovalbumin-induced allergic mice, whereas dietary fiber intake significantly suppressed the allergic responses, attenuated allergic symptoms of nasal rubbing and sneezing, decreased the pathology of eosinophil infiltration and goblet cell metaplasia in the nasal mucosa and lung, inhibited serum OVA-specific IgE levels, and lowered the levels of Th2 cytokines in NALF and BALF, but, increased Th1 (IFN-?) cytokines. Additionally, dietary fiber intake also increased the proportion of Bacteroidetes and Actinobacteria, and decreased Firmicutes and Proteobacteria. Levels of probiotic bacteria, such as Lactobacillus and Bifidobacterium, were upgraded significantly.ConclusionLong-term deficiency of dietary fiber intake increases the susceptibility to AAD, whereas proper fiber supplementation promotes effectively the balance of Th1/Th2 immunity and then attenuates allergic inflammatory responses significantly, as well as optimizes the structure of intestinal microbiota, which suggests potential for novel preventive and therapeutic intervention.

Dataset Information

Superoxide dismutase 3 controls adaptive immune responses and contributes to the inhibition of ovalbumin-induced allergic airway inflammation in mice.

Publications

Superoxide dismutase 3 controls adaptive immune responses and contributes to the inhibition of ovalbumin-induced allergic airway inflammation in mice.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets