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Ganoderma formosanum polysaccharides attenuate Th2 inflammation and airway hyperresponsiveness in a murine model of allergic asthma.

ABSTRACT: Allergic asthma is an inflammatory disease of the airways mediated by Th2 immune responses and characterized by airway hyperresponsiveness (AHR). Fungi of the genus Ganoderma are basidiomycetes that have been used in traditional Asian medicine for centuries. We recently found that PS-F2, a polysaccharide fraction purified from the submerged culture broth of Ganoderma formosanum, stimulates the activation of dendritic cells and primes a T helper 1 (Th1)-polarized adaptive immune response. This study was designed to investigate whether the Th1 adjuvant properties of PS-F2 could suppress the development of allergic asthma in a mouse model. BALB/c mice were sensitized by repeated immunization with chicken ovalbumin (OVA) and alum, followed by intranasal challenge of OVA to induce acute asthma. PS-F2 administration during the course of OVA sensitization and challenge effectively prevented AHR development, OVA-specific IgE and IgG1 production, bronchial inflammation, and Th2 cytokine production. Our data indicate that PS-F2 has a potential to be used for the prevention of allergic asthma.

SUBMITTER: Pi CC

PROVIDER: S-EPMC4072879 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Ganoderma formosanum polysaccharides attenuate Th2 inflammation and airway hyperresponsiveness in a murine model of allergic asthma.

Pi Chia-Chen CC Wang Hui-Yi HY Lu Chiu-Ying CY Lu Frank Leigh FL Chen Chun-Jen CJ

SpringerPlus 20140612

Allergic asthma is an inflammatory disease of the airways mediated by Th2 immune responses and characterized by airway hyperresponsiveness (AHR). Fungi of the genus Ganoderma are basidiomycetes that have been used in traditional Asian medicine for centuries. We recently found that PS-F2, a polysaccharide fraction purified from the submerged culture broth of Ganoderma formosanum, stimulates the activation of dendritic cells and primes a T helper 1 (Th1)-polarized adaptive immune response. This st ...[more]

PMID: 25019045

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Project description:BackgroundAs one of the main functional forms of mesenchymal stem cells (MSCs), MSC-derived extracellular vesicles (MSC-EVs) have shown an alternative therapeutic option in experimental models of allergic asthma. Oxygen concentration plays an important role in the self-renewal, proliferation, and EV release of MSCs and a recent study found that the anti-asthma effect of MSCs was enhanced by culture in hypoxic conditions. However, the potential of hypoxic MSC-derived EVs (Hypo-EVs) in asthma is still unknown.MethodsBALB/c female mice were sensitized and challenged with ovalbumin (OVA), and each group received PBS, normoxic human umbilical cord MSC-EVs (Nor-EVs), or Hypo-EVs weekly. After treatment, the animals were euthanized, and their lungs and bronchoalveolar lavage fluid (BALF) were collected. With the use of hematoxylin and eosin (HE), periodic acid-Schiff (PAS) and Masson's trichrome staining, enzyme-linked immune sorbent assay (ELISA), Western blot analysis, and real-time PCR, the inflammation and collagen fiber content of airways and lung parenchyma were investigated.ResultsHypoxic environment can promote human umbilical cord MSCs (hUCMSCs) to release more EVs. In OVA animals, the administration of Nor-EVs or Hypo-EVs significantly ameliorated the BALF total cells, eosinophils, and pro-inflammatory mediators (IL-4 and IL-13) in asthmatic mice. Moreover, Hypo-EVs were generally more potent than Nor-EVs in suppressing airway inflammation in asthmatic mice. Compared with Nor-EVs, Hypo-EVs further prevented mouse chronic allergic airway remodeling, concomitant with the decreased expression of pro-fibrogenic markers α-smooth muscle actin (α-SMA), collagen-1, and TGF-β1-p-smad2/3 signaling pathway. In vitro, Hypo-EVs decreased the expression of p-smad2/3, α-SMA, and collagen-1 in HLF-1 cells (human lung fibroblasts) stimulated by TGF-β1. In addition, we showed that miR-146a-5p was enriched in Hypo-EVs compared with that in Nor-EVs, and Hypo-EV administration unregulated the miR-146a-5p expression both in asthma mice lung tissues and in TGF-β1-treated HLF-1. More importantly, decreased miR-146a-5p expression in Hypo-EVs impaired Hypo-EV-mediated lung protection in OVA mice.ConclusionOur findings provided the first evidence that hypoxic hUCMSC-derived EVs attenuated allergic airway inflammation and airway remodeling in chronic asthma mice, potentially creating new avenues for the treatment of asthma.

Dataset Information

Ganoderma formosanum polysaccharides attenuate Th2 inflammation and airway hyperresponsiveness in a murine model of allergic asthma.

Publications

Ganoderma formosanum polysaccharides attenuate Th2 inflammation and airway hyperresponsiveness in a murine model of allergic asthma.

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