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Allergic asthma has been considered as a respiratory disorder with pathological features of airway inflammation and remodeling, which involves oxidative stress. Formononetin (FMT) is a bioactive isoflavone obtained from Chinese herb Radix Astragali, and has been reported to have notable anti-inflammatory and antioxidant effects in several diseases. The purpose of our study was to elaborate the effects of FMT on asthma and the underlying mechanisms. To establish allergic asthma model, BALB/c mice were given ovalbumin (OVA) sensitization and challenge, treated with FMT (10, 20, 40 mg/kg) or dexamethasone (2 mg/kg). The effects of FMT on lung inflammation and oxidative stress were assessed. In OVA-induced asthmatic mice, FMT treatments significantly ameliorated lung function, alleviated lung inflammation including infiltration of inflammatory cells, the elevated levels of interleukin (IL)-4, IL-5, and IL-13, immunoglobulin (Ig) E, CC motif chemokine ligand 5 (CCL5, also known as RANTES), CCL11 (also called Eotaxin-1), and IL-17A. In addition, FMT treatments eminently blunted goblet cell hyperplasia and collagen deposition, and remarkably reduced oxidative stress as displayed by decreased reactive oxygen species (ROS), and increased superoxide diamutase (SOD) activity. Furthermore, to clarify the potential mechanisms responsible for the effects, we determined the inflammation and oxidation-related signaling pathway including nuclear factor kappa b (NF-kB), c-Jun N-terminal kinase (JNK), and the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2). FMT treatments appeared to dramatically inhibit the activation of NF-kB and JNK, significantly elevated the expression of heme oxygenase 1 (HO-1) but failed to activate expression of Nrf2. In conclusion, our study suggested that FMT had the therapeutic effects in attenuating airway inflammation and oxidative stress in asthma.

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Asthma is associated with innate and adaptive immunity mediated by immune cells. T cell or macrophage dysfunction plays a particularly significant role in asthma pathogenesis. Furthermore, crosstalk between them continuously transmits proinflammatory or anti-inflammatory signals, causing the immune cell activation or repression in the immune response. Consequently, the imbalanced immune microenvironment is the major cause of the exacerbation of asthma. Here, we discuss the role of T cells, macrophages, and their interactions in asthma pathogenesis.

Previous studies have indicated that allergens such as house dust mites (HDM) in the environment can induce allergic asthma. Ferroptosis is a newly discovered form of regulatory cell death characterized by aberrant lipid peroxidation and the accumulation of reactive oxygen species (ROS) in cells. However, whether ferroptosis participates in the pathological process of asthma remains to be elucidated. The present study used a HDM-induced mouse asthma model to determine the effect of HDM exposure on allergic asthma and its underlying mechanisms. Female BALB/c mice were intranasally exposed to HDM to induce allergic asthma. Airway hyperresponsiveness (AHR), lung inflammation, mucus secretion, IgE levels, cytokine levels and inflammatory cell counts in bronchoalveolar lavage fluid (BALF) were investigated. In addition, the morphological changes of mitochondria, ROS levels, glutathione (GSH) levels and changes in ferroptosis pathway proteins were also determined in murine lungs. As a result, HDM exposure significantly increased AHR, inflammatory cell infiltration and mucus secretion around the airways. Furthermore, elevated IgE levels in the BALF, lung eosinophilia and a concomitant increase in IL-13 and IL-5 levels in BALF were observed. HDM inhalation increased ROS and decreased GSH levels in the lungs. HDM inhalation induced dysmorphic small mitochondria with decreased crista, as well as condensed, ruptured outer membranes. Western blotting demonstrated that the activities of glutathione peroxidase 4 and catalytic subunit solute carrier family 7 member 11 were significantly decreased, and that protein expression levels of acyl-CoA synthetase long-chain family member 4 and 15 lipoxygenase 1 were upregulated compared with mice in the normal control group. Overall, these results indicated that the AHR, airway inflammation, lipid peroxidation and ROS levels increased in HDM-induced asthma, and that HDM inhalation induced ferroptosis in the lungs, which helped to form an improved understanding of the pathogenesis of allergic asthma.

Asthma is a chronic airway inflammatory disorder related to variable expiratory airflow limitation, leading to wheeze, shortness of breath, chest tightness, and cough. Its characteristic features include airway inflammation, airway remodeling and airway hyperresponsiveness. The pathogenesis of asthma remains extremely complicated and the detailed mechanisms are not clarified. Long noncoding RNAs (lncRNAs) have been reported to play a prominent role in asthma and function as modulators of various aspects in pathological progress of asthma. Here, we summarize recent advances of lncRNAs in asthma pathogenesis to guide future researches, clinical treatment and drug development, including their regulatory functions in the T helper (Th) 1/Th2 imbalance, Th17/T regulatory (Treg) imbalance, eosinophils dysfunction, macrophage polarization, airway smooth muscle cells proliferation, and glucocorticoid insensitivity.

Background Group 2 innate lymphoid cells (ILC2s) are known to serve important functions in the pathogenesis of allergic airway inflammation. Studies have shown that acupuncture has an anti-inflammatory effect in the airways. However, how acupuncture treatment affects innate immunity, especially with regard to the function of ILC2s in ovalbumin (OVA)-induced allergic airway inflammation, is poorly understood. Methods BALB/c mice were injected and subsequently challenged with OVA ± treated with manual acupuncture. At the end of the experimental course, lung function was assessed by measurement of airway resistance (RL) and lung dynamic compliance (Cdyn). Cytokine levels were detected by enzyme-linked immunosorbent assay (ELISA). ILC2 proportions in the lung were analyzed by flow cytometry. Results The results showed that airway inflammation and mucus secretion were significantly suppressed by acupuncture treatment. RL decreased while Cdyn increased after acupuncture treatment. There was an apparent decrease in the bronchoalveolar lavage fluid (BALF) concentrations of interleukin (IL)-5, IL-13, IL-9, IL-25 and IL-33 and an increase in soluble IL-33 receptor (sST2) levels compared with untreated asthmatic mice. Acupuncture also reduced the lin–CD45+KLRG1+ST2+ cell proportion in the lung. Conclusion In conclusion, this study has demonstrated that acupuncture treatment alleviates allergic airway inflammation and inhibits pulmonary ILC2 influx and IL-5, IL-9 and IL-13 production. The inhibition of ILC2s by acupuncture may be associated with the IL-33/ST2-signaling pathway and IL-25 levels, thereby offering protection from the respiratory inflammation associated with asthma.

Allergic asthma is well known as a common respiratory disorder comprising an allergic inflammatory nature and excessive immune characteristic. N6-methyladenosine (m6A) methylation is an RNA epigenetic modification that post-transcriptionally regulates gene expression and function by affecting the RNA fate. Currently, m6A methylation is gaining attention as a mechanism of immunoregulation. However, whether m6A methylation engages the pathological process of asthma remains uncertain. Here, we present the m6A methylomic landscape in the lung tissues of ovalbumin-induced acute asthma mice using MeRIP-seq and RNA-seq. We identified 353 hypermethylated m6A peaks within 329 messenger RNAs (mRNAs) and 150 hypomethylated m6A peaks within 143 mRNAs in the lung tissues of asthmatic mice. These differentially methylated mRNAs were found to be involved in several immune function-relevant signaling pathways. In addition, we predicted 25 RNA-binding proteins that recognize the differentially methylated peak sites by exploring public databases, and the roles of these proteins are mostly related to mRNA biogenesis and metabolism. To further investigate the expression levels of the differentially methylated genes, we performed combined analysis of the m6A methylome and transcriptome data and identified 127 hypermethylated mRNAs (107 high and 20 low expression) and 43 hypomethylated mRNAs with differential expressions (9 high and 34 low expression). Of these, there are a list of mRNAs involved in immune function and regulation. The present results highlight the essential role of m6A methylation in the pathogenesis of asthma.