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?5i subunit deficiency of the immunoproteasome leads to reduced Th2 response in OVA induced acute asthma.

ABSTRACT: The immunoproteasome subunit ?5i has been shown to play an important role in Th1/Th17 driven models of colitis and arthritis. However, the function of ?5i in Th2 dependent diseases remains enigmatic. To study the role of ?5i in Th2-driven pathology, ?5i knockout (KO) and control mice were tested in different models of experimental allergic asthma. ?5i-deficient mice showed reduced OVA/Alum- and subcutaneous/OVA-induced acute asthma with decreased eosinophilia in the bronchoalveolar lavage (BAL), low OVA-specific IgG1 and reduced local and systemic Th2 cytokines. While Th2 cells in the lungs were reduced, Tregs and Th1 cells were not affected. Attenuated asthma in ?5i KO mice could not be attributed to defects in OVA uptake or maturation of dendritic cells in the lung. Surprisingly, ?5i deficient mice developed HDM asthma which was comparable to control mice. Here, we present novel evidence for the requirement of the ?5i immunosubunit to generate a strong Th2 response during OVA- but not HDM-induced acute asthma. The unexpected role of ?5i in OVA asthma remains to be clarified.

SUBMITTER: Volkov A

PROVIDER: S-EPMC3617144 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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β5i subunit deficiency of the immunoproteasome leads to reduced Th2 response in OVA induced acute asthma.

Volkov Anton A Hagner Stefanie S Löser Stephan S Alnahas Safa S Raifer Hartmann H Hellhund Anne A Garn Holger H Steinhoff Ulrich U

PloS one 20130404 4

The immunoproteasome subunit β5i has been shown to play an important role in Th1/Th17 driven models of colitis and arthritis. However, the function of β5i in Th2 dependent diseases remains enigmatic. To study the role of β5i in Th2-driven pathology, β5i knockout (KO) and control mice were tested in different models of experimental allergic asthma. β5i-deficient mice showed reduced OVA/Alum- and subcutaneous/OVA-induced acute asthma with decreased eosinophilia in the bronchoalveolar lavage (BAL), ...[more]

PMID: 23593249

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Project description:BackgroundLoki zupa (Luooukezupa) decoction, consisting of the roots of Hyssopuscuspidatus Boriss (Shenxiangcao) and Irishalophila Pall root (Yuanweigen), is commonly used in Uygur medicine to treat asthma. However, the mode of action of this material has yet to be elucidated. This study aims to investigate the effects of Loki zupa decoction on the airway inflammation of an ovalbumin (OVA)-induced asthma mouse model.MethodsMice were divided into normal control (NC), asthma (A), high, medium and low doses of Loki zupa decoction (L 14.0, L 7.0, L 3.5), water extract (LW), n-butanol extract (LN), ethyl acetate extract (LE) and dexamethasone (DEX) groups. Antiasthmatic model was induced by OVA sensitization and challenged using BALB/c mice. Airway hyperresponsiveness (AHR) toward methacholine (Mch) was assessed using Buxco equipment. Lung inflammation was measured by hematoxylin and eosin staining and bronchoalveolar lavage fluid (BALF) cell count and classification. Inflammatory cytokines in BALF and serum were analyzed by Bio-Plex assay, and mRNA levels were investigated by qPCR analysis. The roots of H. Boriss (250 g) and I. Pall (250 g) were decocted, concentrated and diluted to 14.0, 7.0 and 3.5 g crude herb/kg body weight. The LW, LN and LE of the Loki zupa decoction were prepared and diluted to a dose equivalent to 7 g of crude herb/kg body weight.ResultsLoki zupa decoction and its extracts significantly attenuated the AHR towards Mch (all P < 0.05). Treatment with Loki zupa decoction and its extracts relieved the infiltration of inflammatory cells in and around the airways, and reduced the total white blood cell (all P < 0.05), neutrophil (all P < 0.05), monocyte (all P < 0.05) and eosinophil (all P < 0.05) counts in the BALF. The BALF samples collected from the mice treated with the Loki zupa decoction and its extracts had lower levels of IL-1β (all P < 0.05), TNF-α (all P < 0.05), IL-2 (all P < 0.05), IL-4 (P = 0.047) and IL-5 (all P < 0.05). The serum samples of these mice also had lower IL-1β (all P < 0.05), TNF-α (all P < 0.05), IL-4 (all P < 0.05) and IL-5 (all P < 0.05) levels and higher levels of IFN-γ (P < 0.001) compared with the OVA-induced asthma mouse model. qPCR analysis revealed that Loki zupa decoction and its extracts inhibited mRNA expression of IL-4 (all P < 0.05), IL-5 (all P < 0.05) and IL-13 (all P < 0.05) and promoted mRNA expression of IFN-γ (all P < 0.05) in asthmatic mice.ConclusionLoki zupa decoction reduced AHR, attenuated airway inflammation, promoted Th1 and suppressed Th2 cell functions in an OVA-induced asthma mouse model.

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?5i subunit deficiency of the immunoproteasome leads to reduced Th2 response in OVA induced acute asthma.

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β5i subunit deficiency of the immunoproteasome leads to reduced Th2 response in OVA induced acute asthma.

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