Bacillus subtilis KCTC 11782BP-Produced Alginate Oligosaccharide Effectively Suppresses Asthma via T-Helper Cell Type 2-Related Cytokines

Abstract

According to the World Health Organization in 2013, 235 million people are afflicted with asthma. Asthma is a severe pulmonary disease that can be caused by the imbalance of T-helper (Th) type 1 (Th1) and type 2 (Th2) cells, and it is potentially fatal. In this study, we evaluated the anti-asthmatic effect of alginate oligosaccharide (AO), which was prepared from seaweed and converted by Bacillus subtilis KCTC 11782BP, in the mouse model of ovalbumin (OVA)-induced asthma. BALB/c mice were divided into the vehicle control (sensitized but not challenged), asthma induction, positive control (1 mg/kg dexamethasone), 50 mg/kg/day AO-treated, 200 mg/kg/day AO-treated, and 400 mg/kg/day AO-treated groups. The numbers or levels of inflammatory cells, eosinophils, and immunoglobulin (Ig) E were measured in bronchoalveolar lavage fluid (BALF), and asthma-related morphological and cytokine changes were analyzed in lung tissues. Our results show that AO dramatically reduced inflammatory cell numbers, eosinophil count, and IgE levels in BALF, and it dose-dependently inhibited asthmatic histopathological changes in the lung. In addition, AO dose-dependently suppressed the expression of CD3+ T-cell co-receptors, CD4+ Th cells, CD8+ cytotoxic T-cell-related factors, macrophages, and MHCII class. AO dose-dependently decreased the expression levels of Th1/2 cells-regulatory transcription factors such as GATA-3 which modulates Th2 cell proliferation and T-bet which does Th1 cell proliferation. The mRNA levels of all Th1/2-related cytokines, except IL-12α, were dose-dependently suppressed by AO treatment. In particular, the mRNA levels of IL-5, IL-6, and IL-13 were significantly inhibited by AO treatment. Our findings suggest that AO has the potential to be an anti-asthmatic drug candidate, due to its modulation of Th1/Th2 cytokines, which contribute to the pathogenesis of asthma.

Alginate Oligosaccharide Prevents Acute Doxorubicin Cardiotoxicity by Suppressing Oxidative Stress and Endoplasmic Reticulum-Mediated Apoptosis

“…The plasma level of cTnI was significantly elevated in the DOX-treated mice, whereas AOS pretreatment down-regulated this increase, indicating the strong cardioprotective efficacy against acute DOX cardiotoxicity. AOS has also been shown to provide protection against many diseases including Alzheimer’s disease and asthma [22,23]. By using neuron-like PC12 cells, Tusi et al previously showed that AOS decreased H2O2-induced oxidative stress and endoplasmic reticulum-mediated apoptosis [12].…”

Opuntia humifusamodulates morphological changes characteristic of asthma via IL-4 and IL-13 in an asthma murine model

“…Histopathological analysis was conducted as previously described [28]. Lung tissues were fixed in 10% (v/v) formaldehyde solution, dehydrated in a graded ethanol series (99.9%, 90%, 80%, and 70%), and embedded in paraffin.…”

“…IHC analysis was conducted as previously described [28]. Deparaffinized tissue sections were treated with 3% hydrogen peroxide in methanol for 10 min to remove endogenous peroxidase.…”

Alginate Oligosaccharides: Production, Biological Activities, and Potential Applications

“…The enzymes secreted by these Bacteroidetes hydrolyze alginate (Li, Shang, Li, Wang, & Yu, ). Alginate‐degrading bacteria, such as Gracilibacillus A7 (Tang, Taniguchi, Chu, Zhou, & Nagata, ), Bacillus subtilis KCTC 11782BP (Bang et al., ; Yang et al., ), Bacillus litoralis strain M3 (Wang, Chen et al., ), Flavobacterium sp. strain LXA (An et al., ), and Pseudoalteromonas agarovorans CHO‐12 (Choi, Piao, Shin, & Cho, ), have been isolated and utilized for AOS production.…”

“…Asthma is a potentially fatal pulmonary disease caused by the imbalance of Th1 and Th2 cells. AOS produced through Bacillus subtilis KCTC 11782BP conversion modulated secretion of Th1/Th2 cytokines in the BALB/c mouse model of ovalbumin‐induced asthma, indicating potential for AOS as an antiasthmatic drug candidate (Bang et al., ). GAOS generated from brown seaweed Laminaria hyperborea (90% to 95% of G residues and average MW of 2,600 Da) bound with mucin, resulting in disrupted mucin interaction and expansion.…”