Lipopolysaccharide Exposure Alleviates Asthma in Mice by Regulating Th1/Th2 and Treg/Th17 Balance

Abstract

BackgroundIt is generally believed that endotoxin exposure exacerbates risk of developing asthmatic symptoms. However, recent studies have indicated that prior bacterial exposure may prevent future symptoms of asthma. Here, we evaluated the influence of pre-exposure to different concentrations of lipopolysaccharide (LPS) to subsequent ovalbumin (OVA) allergen sensitization and challenge.Material/MethodsFour-week-old Balb/c mice were treated intranasally with varying concentrations of LPS (1 ug, 10 ug, and 100 ug) or sterile PBS for 10 days, then 2 weeks later they were exposed to OVA. Both the molecular and functional airway responses to OVA administration were assessed following prior exposure to different doses of LPS or controls. Additionally, the Th1/Th2 and Treg/Th17 balance was measured.ResultsAirway responsiveness and immune cell recruitment in the bronchoalveolar lavage (BALF) were decreased in animals exposed to a low dose of LPS (1 ug) treatment compared with the asthma group. Moderate-dose (10 ug) and high-dose (100 ug) LPS administration showed no differences from controls. Further, low-dose LPS (1 ug) exposure was associated with increased Th1 cytokines, T-bet, Treg cytokine (IL-10, TGF-β), and Foxp3 expression, but decreased Th2 cytokines (IL-4,5,13), GATA3, Th17, and ROR-γt expression compared with the asthma group. Finally, higher numbers of CD4+CD25+Foxp3+Treg cells, and CD4+INF-γ+T cells, and lower CD4+IL-4+T cells and CD4+IL-17+T cells were observed in the low-dose LPS-treated groups compared to controls.ConclusionsOur findings suggest that prior exposure to low doses of LPS may protect from OVA-induced airway hyperresponsiveness (AHR) and histopathologic changes through regulation of the Th1/Th2 and Treg/Th17 balance.

Suppression of sirtuin 1 alleviates airway inflammation through mTOR‑mediated autophagy

“…A Th1/Th2 imbalance is believed to play a vital role in asthma pathogenesis, including changes in the levels of Th1 cytokines (IFN-γ) and Th2 cytokines (IL-4 and IL-13) ( 2 ). To determine the effects of EX-527 on cytokine release in OVA-induced asthmatic mice, BALF IL-4, IL-13 and IFN-γ levels normalized to total protein amounts in BALF were evaluated by ELISA 24 h after the final OVA challenge.…”

“…Allergic asthma is one of the most common chronic inflammatory disorders characterized by airway hyperresponsiveness and increased infiltration of inflammatory cells, especially eosinophils, into the airways and lungs (1). The T helper cell (Th)2 immune response and associated cytokines, such as il-4, il-5 and il-13, are known to play important roles in the pathogenesis of asthma (2). a total of seven sirtuin (SirT) family members have been identified in mammals, termed SIRT1 to SIRT7 (3).…”

Targeted inhibition of β-catenin alleviates airway inflammation and remodeling in asthma via modulating the profibrotic and anti-inflammatory actions of transforming growth factor-β1

“…In addition to remodeling, another critical feature of asthma is airway in ammation. A recent report indicates that Th17 cells and Tregs have a signi cant role in asthma [24]. The Th17 cells secrete IL-17 and mediate the occurrence and progression of inflammatory reactions.…”

Targeted inhibition of β-catenin alleviates airway inflammation and remodeling in asthma via modulating the profibrotic and anti-inflammatory actions of transforming growth factor-β1

“…Reports indicate that Th2 cells, Th17 cells and Tregs have a significant role in asthma. 26 Asthma is classically recognized as a typical Th2 cells disease, in which the inflammatory process is dominated by Th2 cells that release the cytokines IL-4, IL-5, and IL-13. These cytokines modulate airway inflammation by activating EOSs and IgE production.…”