Airway Inflammation In Asthmatic Mice Research Articles

Chemical Characterization and Potential Mechanism of the Anti-Asthmatic Activity of a Subfraction from Schisandra chinensis Fruit Extract.

Schisandra chinensis fruit is a widely edible and medicinal resource, whose extract had a good inhibitory effect on airway inflammation in asthmatic mice. However, the main active components remain unknown. In this work, we found that PET2, a subfraction of its ethanolic extract petroleum ether, displayed significant anti-inflammatory effects in interleukin (IL)-4/tumor necrosis factor (TNF)-α-stimulated BEAS-2B cells. Meanwhile, in the ovalbumin (OVA)-induced allergic asthma mice model, PET2 (200 and 400 mg/kg) had significant effects on attenuating airway inflammatory cell infiltration and reducing serum Th2-related cytokines. Further studies led to the isolation and identification of 14 compounds, guided by ultraperformance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS)-based rapid characterization of chemical constituents. Combining network pharmacology analysis and in vitro experiments, we found that six compounds from PET2 had good anti-inflammatory properties. The potential mechanism may be involved in Fc epsilon RI, T cell receptor, and Jak-STAT signaling pathways. This study clarified the anti-inflammatory properties of the main active fraction and active compounds of S. chinensis fruit and provided a theoretical basis for its anti-asthma scientific utilization.

PM2.5 aggravates airway inflammation in asthmatic mice: activating NF-κB via MyD88 signaling pathway

ABSTRACT The role of PM2.5 in the bronchial asthma remains unclear. In this study, the deficient mice of TLR4-/-, TLR2-/- and MyD88 -/- were used to establish asthma model. The effects of PM2.5 on the inflammatory response in lung tissue of these mice were observed. PM2.5 increased alveolar macrophages and neutrophils, up-regulated the IL-12 and KC expression in WT mice, but down-regulated their levels in TLR2 -/-, TLR4 -/- and MyD88 -/- mice. OVA+PM2.5 stimulated neutrophil count in WT mice, but it decreased in TLR2 -/- and TLR4 -/- mice. OVA+PM2.5 also increased the Eotaxin, IL-5, IL-13 and MCP-3 expression levels, and OVA specific IgE and IgG1 in serum also increased in WT group. PM2.5 may activate NF-κB through the TLR2/TLR4/MyD88 signaling pathway and aggravate allergic inflammation of lung in asthmatic mice. The microelements in PM2.5 granules, such as lipopolysaccharide, may be an important factor in the high incidence of asthma.

An exopolysaccharide from Bacillus subtilis alleviates airway inflammatory responses via the NF-κB and STAT6 pathways in asthmatic mice.

Bacillus subtilis is an intestinal probiotic for immune homeostasis and its exopolysaccharide (EPS) is known to possess anti-inflammatory and antioxidant properties. The underlying mechanisms are not yet fully understood. In the present study, we investigated the effects of the EPS (50, 100, 200 mg/kg) on airway inflammation in asthmatic mice. Our results showed that EPS treatment of asthmatic mice significantly alleviated pathological damage in the lungs, remarkably decreased the counts of total inflammatory cells including lymphocytes, and eosinophils in the bronchoalveolar lavage fluid (BALF) and reduced indexes of oxidative damage. Moreover, the expression of type II T-helper cell (Th2) cytokines (interleukin- (IL)4 and -5) subsequent to EPS treatment was found to be dramatically down-regulated in a concentration-dependent manner. Additionally, the EPS treatment reduced JAK1, STAT6 and nuclear factor-κB (NF-κB) expression in the lungs of asthmatic mice. Taken together, these results suggest that the EPS from B. subtilis alleviates asthmatic airway inflammation, which involves the reduction in reactive oxygen species (ROS) and the down-regulation of the STAT6 and NF-κB inflammatory pathways, which can further reduce Th2 cytokine expression and eosinophilic inflammation. Thus, our findings provide a potential mechanism through which the EPS mitigates asthma, suggesting that the EPS could be a potential source of an anti-asthmatic drug.

Anthocyanins Inhibit Airway Inflammation by Downregulating the NF-κB Pathway via the miR-138-5p/SIRT1 Axis in Asthmatic Mice

Objective: Asthma, caused by chronic inflammation, is a common disease. Anthocyanins are involved in asthma treatment. This study explored the mechanism of anthocyanins on airway inflammation in asthmatic mice by regulating nuclear factor-κB (NF-κB) via the miR-138-5p/sirtuin-1 (SIRT1) axis. Methods: The asthmatic mouse model was established by ovalbumin (OVA) induction and treated with anthocyanins or simultaneously injected with the lentivirus miR-138-5p mimic, followed by the measurement of lung inflammatory injury and IL-4, IL-5, IL-13, and IFN-γ levels in bronchoalveolar lavage fluid. Human bronchial epithelial (HBE) cells 16HBE14o-160 were induced by OVA to establish an asthmatic cell model, treated with anthocyanins and manipulated with miR-138-5p mimic and pcDNA3.1-SIRT1. The releases of inflammatory cytokines, the nuclear translocation of p-p65/p65 in the NF-κB pathway, and the levels of miR-138-5p and SIRT1 mRNA were detected. Results: In vivo experiments showed that anthocyanins could reduce the OVA-induced airway hyperresponsiveness and airway inflammation, improve the inflammatory infiltration and mucus in lung tissues, and diminish the miR-138-5p level in asthmatic mice. Infection with the miR-138-5p mimic averted the remission effect of anthocyanins in asthmatic mice. In vitro experiments showed that in HBE cells exposed to OVA, anthocyanins reduced the miR-138-5p level, increased the SIRT1 level, inhibited the release of inflammatory factors, and reduced the nuclear translocation of NF-κB p65. miR-138-5p targeted SIRT1. miR-138-5p overexpression partially reversed the therapeutic effect of anthocyanins, while SIRT1 overexpression antagonized the effect of miR-138-5p overexpression. Conclusion: Anthocyanins inhibited the NF-κB pathway by regulating the miR-138-5p/SIRT1 axis, thus inhibiting airway inflammation in asthmatic mice.

Sodium houttuynia alleviates airway inflammation in asthmatic mice by regulating FoxP3/RORγT expression and reversing Treg/Th17 cell imbalance

Synthetized from a natural oil of Houttuynia cordata, sodium houttuynia was reported to have anti-inflammatory effects. The present study aimed to investigate whether sodium houttuynia could alleviate the characteristic airway inflammation and Treg/Th17 cell imbalance of asthma in vivo. Experimental mice with neutrophilic asthma were injected with sodium houttuynia or dexamethasone (alone or in combination) intraperitoneally. The airway reactivity was measured, and bronchoalveolar lavage fluid was collected for cell count. Hematoxylin/eosin and periodic acid–Schiff staining were performed to assess pulmonary inflammation and mucus hypersecretion. Immunohistochemical analysis was conducted to determine the expression of IL-10, IL-17A, FoxP3, and RORγT in the lung tissue, and the serum levels of IL-10 and IL-17A were analyzed by ELISA. The proportion of CD4+CD25+FoxP3+ Treg and Th17 cells within the CD4+ T cell subset of splenocytes was analyzed by flow cytometry. FoxP3 and RORγT mRNA and protein expressions in the lung were analyzed by real-time PCR and western blot, respectively. Overall, sodium houttuynia was found to ameliorate the Treg/Th17 cell imbalance and reduce the airway inflammation, hyperresponsiveness, and mucus hypersecretion by increasing the frequency of CD4+CD25+FoxP3+ Treg cells and the secretion of IL-10, while decreasing the proportion of Th17 cells and IL-17A production. Although the regulatory effect of sodium houttuynia was not as good as that achieved with dexamethasone, combination of the two compounds showed improved inhibitory effects on airway hyperresponsiveness, inflammation, and mucus hypersecretion. Hence, sodium houttuynia may be beneficial for the treatment of asthma.

Salidroside Mitigates Airway Inflammation in Asthmatic Mice via the AMPK/Akt/GSK3β Signaling Pathway

Introduction: This study aimed to explore the effects and mechanisms of salidroside (SAL) in airway inflammation in asthmatic mice. Methods: Mice were sensitized with ovalbumin (OVA) to establish an asthma model. They were divided into the control group, OVA group, SAL low-dose group (SAL-L), SAL high-dose group (SAL-H), and dexamethasone (DXM) group. The airway reactivity of the mice was measured, and the total cells, neutrophils, eosinophils, and lymphocytes were counted, respectively. The levels of IL-4, IL-5, IL-13, and IFN-γ in bronchoalveolar lavage fluid (BALF) were detected by ELISA. Immunohistochemistry was used to detect the expression levels of p-AMPK, p-Akt, and p-GSK3β. Western blot was used to detect cytokine levels in lung tissue and p-AMPK, p-Akt, and p-GSK3β levels in LPS-induced 16HBE cells. Results: The airway hyperresponsiveness of asthmatic mice in the SAL-H group decreased (p < 0.05), and the total number of cells, neutrophils, eosinophils, and lymphocytes decreased significantly (p < 0.05). In addition, the airways of mice showed airway inflammatory infiltration and goblet cell proliferation, and the corresponding cellular inflammatory factors IL-4, IL-5, and IL-13 were significantly decreased. However, the expression of IFN-γ in BALF and lung tissues was increased (p < 0.05). Moreover, after the mice were treated with SAL, the phosphorylation level of AMPK was significantly increased, which further reduced the phosphorylation levels of Akt and GSK3β (p < 0.05). Both SAL and AMPK inhibitors exerted effects on LPS-induced 16HBE cells, consistent with in vivo results. Conclusion: SAL can inhibit bronchial hyperresponsiveness and reduce tracheal inflammation by increasing AMPK phosphorylation and inhibiting Akt and GSK3β signaling pathways.

SJMHE1 Peptide from Schistosoma japonicum Inhibits Asthma in Mice by Regulating Th17/Treg Cell Balance via miR-155.

PurposeHelminths and their products can regulate immune response and offer new strategies to control and alleviate inflammation, including asthma. We previously found that a peptide named as SJMHE1 from Schistosoma japonicum can suppress asthma in mice. This study mainly investigated the molecular mechanism of SJMHE1 in inhibiting asthma inflammation.MethodsSJMHE1 was administered to mice with OVA-induced asthma via subcutaneous injection, and its effects were detected by testing the airway inflammation of mice. The Th cell distribution was analyzed by flow cytometry. Th-related transcription factor and cytokine expression in the lungs of mice were analyzed using quantitative real-time PCR (qRT-PCR). The expression of miR-155 and levels of phosphorylated STAT3 and STAT5 were also determined after SJMHE1 treatment in mice by qRT-PCR and Western blot analysis. The in vitro mouse CD4+ T cells were transfected with lentivirus containing overexpressed or inhibited miR-155, and the proportion of Th17, Treg cells, CD4+p-STAT3+, and CD4+p-STAT5+ cells were analyzed by flow cytometry.ResultsSJMHE1 ameliorated the airway inflammation of asthmatic mice, upregulated the proportion of Th1 and Treg cells, and the expression of Th1 and Treg-related transcription factor and cytokines. Simultaneously, SJMHE1 treatment reduced the percentage of Th2 and Th17 cells and the expression of Th2 and Th17-related transcription factor and cytokines. SJMHE1 treatment decreased the expression of miR-155 and p-STAT3 but increased p-STAT5 expression. In vitro, the percentage of Th17 and CD4+p-STAT3+ cells increased in CD4+ T cells transfected over-expression of miR-155, but SJMHE1 inhibited the miR-155-mediated increase of Th17 cells. Furthermore, SJMHE1 increased the proportion of Treg and CD4+p-STAT5+ cells after transfected over-expression or inhibition of miR-155.ConclusionSJMHE1 regulated the balance of Th17 and Treg cells by modulating the activation of STAT3 and STAT5 via miR-155 in asthma. SJMHE1 might be a promising treatment for asthma.

Cycloastragenol alleviates airway inflammation in asthmatic mice by inhibiting autophagy.

Cycloastragenol (CAG), a secondary metabolite from the roots of Astragalus zahlbruckneri, has been reported to exert anti-inflammatory effects in heart, skin and liver diseases. However, its role in asthma remains unclear. The present study aimed to investigate the effect of CAG on airway inflammation in an ovalbumin (OVA)-induced mouse asthma model. The current study evaluated the lung function and levels of inflammation and autophagy via measurement of airway hyperresponsiveness (AHR), lung histology examination, inflammatory cytokine measurement and western blotting, amongst other techniques. The results demonstrated that CAG attenuated OVA-induced AHR in vivo. In addition, the total number of leukocytes and eosinophils, as well as the secretion of inflammatory cytokines, including interleukin (IL)-5, IL-13 and immunoglobulin E were diminished in bronchoalveolar lavage fluid of the OVA-induced murine asthma model. Histological analysis revealed that CAG suppressed inflammatory cell infiltration and goblet cell secretion. Notably, based on molecular docking simulation, CAG was demonstrated to bind to the active site of autophagy-related gene 4-microtubule-associated proteins light chain 3 complex, which explains the reduced autophagic flux in asthma caused by CAG. The expression levels of proteins associated with autophagy pathways were inhibited following treatment with CAG. Taken together, the results of the present study suggest that CAG exerts an anti-inflammatory effect in asthma, and its role may be associated with the inhibition of autophagy in lung cells.

Long non-coding RNA NKILA alleviates airway inflammation in asthmatic mice by promoting M2 macrophage polarization and inhibiting the NF-κB pathway

Asthma remains a severe public health problem. Long non-coding RNAs (lncRNAs) are potent regulators in various diseases including asthma. This study investigated the mechanism of lncRNA NF-κB interacting lncRNA (NKILA) in asthma. The model of asthma in mice was induced by ovalbum (OVA). LncRNA NKILA expression, serum total IgE level and expressions of inflammatory cytokines (IL-4, IL-5, IL-13, and TNF-α) in OVA-induced asthmatic mice were detected. NKILA was overexpressed to evaluate the airway inflammation and airway hyperresponsiveness (AHR) in asthmatic mice. Macrophage abundance, M1/M2-polarized macrophage numbers, and expressions of macrophage polarization-related genes were detected. Levels of the NF-κB pathway-related proteins were determined. Downregulated NKILA and upregulated total IgE level and expressions of inflammatory cytokines were observed in asthmatic mice. NKILA overexpression alleviated AHR and airway inflammation in asthmatic mice. NKILA reduced macrophage abundance and promoted M2 macrophage polarization in asthmatic mice. NKILA inhibited the NF-κB pathway in asthmatic mice. We highlighted that lncRNA NKILA limited the asthmatic airway inflammation via promoting M2 macrophage polarization and inhibiting the NF-κB pathway.

Therapeutic efficacy of chitosan nanoparticles loaded with BCG-polysaccharide nucleic acid and ovalbumin on airway inflammation in asthmatic mice.

In this study, immunoregulation and desensitization therapies were jointly applied in the treatment of asthma, in which chitosan (CS) nanoparticles were used. BALB/c mice were selected and mouse models of asthma were constructed. Mice were divided into 7 groups. A double-chamber plethysmograph, MTT, hematoxylin-eosin staining, and ELISA were used. The expression levels of IL-4 and IL-5 in lung tissue cells were detected. CS-BCG-PSN-OVA sustained-release vaccines significantly alleviated airway hyperresponsiveness (AHR) in asthmatic mice. The numbers of total lymphocytes and eosinophils in BALF were remarkably reduced. The expression levels of IL-4 and IL-5 in lung tissue cells of the treatment groups were dramatically decreased. CS-BCG-PSN-OVA was found in vitro to be able to inhibit OVA-induced T-cell proliferation and upregulate the proportion of CD4+CD25+Foxp3+ T cells. CS-BCG-PSN-OVA sustained-release vaccine could significantly attenuate AHR and airway inflammation in asthmatic mice. Thus, it has a promising application prospect for the treatment of bronchial asthma.

Airway exposure to perfluorooctanoate exacerbates airway hyperresponsiveness and downregulates glucocorticoid receptor expression in asthmatic mice.

BackgroundMultiple environmental risk factors play a vital role in the pathogenesis of asthma, which contribute to the phenotypic expression of asthma. Perfluorooctanoate (PFOA) is the most common and abundant perfluorocarbon (PFC) in humans, and it has been detected in water and the atmosphere worldwide. Glucocorticoid receptor (GR) is considered to exert a protective effect on asthma and is associated with the sensitivity to glucocorticoids. Dermal or oral exposure to PFOA has been shown to contribute various effects on airway inflammation in individuals with ovalbumin (OVA)-induced asthma. Notably, airway exposure has a critical contribution to the pathogenesis of asthma. However, the effect of airway exposure to PFOA on airway hyperresponsiveness (AHR) in patients with asthma is not currently understood.MethodsBALB/c mice were administered OVA to induce asthma. PFOA was then administered intratracheally to OVA-induced mice for seven days. Then we assessed the effect of airway exposure to PFOA on AHR and the regulation of the GR expression in asthmatic mice.ResultsThe results showed aggravated AHR and T helper type 2 (Th2) airway inflammation in asthmatic mice. Furthermore, these mice show a substantial decrease in the expression of the GR mRNA and protein.ConclusionsThese data strongly suggest that acute airway exposure to PFOA leads to Th2-related AHR and decreases GR expression, which may increase the difficulty in the treatment of asthma.

Hypoxic hUCMSC-derived extracellular vesicles attenuate allergic airway inflammation and airway remodeling in chronic asthma mice

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.

MiR-135a inhibits airway inflammatory response in asthmatic mice via regulating JAK/STAT signaling pathway.

The objective of this study was to investigate the inhibitory effect of miR-135a in regulating JAK/STAT signaling pathway on airway inflammation in asthmatic mice. An asthma model was established by sensitization and stimulation with ovalbumin (OVA), and the corresponding drug intervention was given from the day of stimulation by means of nasal drops. Airway hyperresponsiveness was tested. The content of miR-135a in the lung tissue of mice was detected by RT-PCR. The pathological changes of lung tissue were evaluated by HE staining. Tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-5, and eotaxin in bronchoalveolar lavage fluid (BALF) and lung tissue were detected by ELISA and immunohistochemistry, respectively. The expression of JAK/STAT signaling pathway-related protein in lung tissue was detected by western blot. To further validate the effect of miR-135a overexpression on the JAK/STAT signaling pathway, pathway activators and inhibitors were added. Compared with the OVA group, the airway hyperresponsiveness of the mice was significantly decreased after treatment with the miR-135a agonist. The expression of miR-135a was significantly increased in the lung tissue and the pathological changes of the lung tissue were alleviated. The contents of TNF-α, IL-6, IL-5, and eotaxin in BALF and lung tissues were decreased. The expression of JAK/STAT signaling pathway-related proteins p-JAK3/JAK3, p-STAT1/STAT1, and p-STAT3/STAT3 were significantly reduced in lung tissue (P<0.05). Addition of JAK inhibitor AG490 reduced airway inflammation in asthmatic mice. miR-135a agonists inhibit airway inflammation in asthmatic mice by regulating the JAK/STAT signaling pathway.

Tetrahydrocurcumin alleviates allergic airway inflammation in asthmatic mice by modulating the gut microbiota

Dietary factors can reshape the gut microbiota and consequently affect disease progression. We previously reported that tetrahydrocurcumin (THC), the major active metabolite of curcumin (Cur), could ameliorate allergic inflammation in asthmatic mice. Herein, we aimed to investigate whether THC or Cur exerts anti-inflammatory effects on allergic asthma via modulating gut microbiota. Ovalbumin (OVA)-induced asthmatic mice were treated with Cur or THC, and the gut microbiota profiles were analyzed by 16S rRNA sequencing. Fecal microbiota transplantation (FMT) from Cur- or THC-fed donor mice was administered to OVA-induced asthmatic mice. Nasal symptoms and inflammation patterns of lungs and colons were evaluated in control, OVA-induced and Cur-or THC-treated mice. Both Cur and THC treatment could alter the compositions of the gut microbiota in asthmatic mice, characterized by a significant decrease in the ratio of Firmicutes to Bacteroidetes; Cur or THC supplementation also reduced the relative abundances of pro-inflammatory bacteria, e.g., Proteobacteria, Intestinimonas, Unidentified-Ruminococcaceae, and Lachnospiraceae, in OVA-induced mice. The relative abundances of Unidentified-Ruminococcaceae, Romboutsia, Intestinimonas, Akkermansia, and Mucispirillum were positively associated with the levels of Th2-related factors in asthmatic mice upon Cur or THC treatment. Moreover, THC-FMT showed better preventive effects than Cur-FMT on the development of allergic inflammation in OVA-induced mice, resulting in a reduction in symptoms and Th2-mediated inflammation in both lung and colon tissues. The results reveal that Cur- or THC-mediated alleviation of airway allergic inflammation is dependent on gut microbiota modulation. THC-induced gut microbiota may have therapeutic potential for asthma treatment.

Perfluorooctanesulfonate and perfluorooctanoate exacerbate airway inflammation in asthmatic mice and in vitro

Emerging evidence suggests associations between Perfluoroalkyl substances (PFASs) exposure and asthma, but the findings are inconsistent. The current study sought to investigate whether perfluorooctanesulfonate (PFOS) and perfluorooctanoate (PFOA) could contribute to asthma exacerbation and to clarify the underlying biological mechanisms. The objectives are a) to determine whether PFOS or PFOA could aggravate the mouse asthma and pulmonary inflammation b) to investigate whether PFOS and PFOA regulate the balance of Th1/Th2 through the JAK-STAT signaling pathway and aggravated asthma. Ovalbumin (OVA) induced asthmatic mice were exposed to PFOS or PFOA by gavage. PFOS and PFOA serum level and toxicity in organs were assessed; and the impacts on respiratory symptoms, lung tissue pathology, T helper cell (Th2) response, and STAT6 pathway activity were also evaluated. In vitro Jurkat cells were used to study the mechanisms of PFOS and PFOA mediated Th1 and Th2 responses. Both PFOS and PFOA exacerbated lung tissue inflammation (greater number of eosinophils and mucus hyperproduction), upregulated Th2 cytokine production (IL-4 and IL-13), and promoted Th2 cells and STAT6 activation. Furthermore, PFOS and PFOA enhanced the Th2 response in Jurkat cells via STAT6 activation; and the effect of PFOS exposure on GATA-3, IL-4 and IFN-γ was blocked after the expression of STAT6 was suppressed in Jurkat cells, however, the effects of PFOA exposure were only partially blocked. PFOS and PFOA aggravated inflammation among OVA-induced asthmatic mice, by promoting the Th2 response in lymphocytes and disturbing the balance of Th1/Th2 through the JAK-STAT signaling pathway.

Anti-Contractile and Anti-Inflammatory Effects of Diacerein on Isolated Mouse Airways Smooth Muscle and Mouse Asthma Model.

Characterized by abnormal smooth muscle contractility and airway inflammation, asthma is one of the most common airway diseases worldwide. Diacerein is a well-known anti-inflammatory drug, widely used in osteoarthritis. In current study, the innovative usage of diacerein in anti-contractile and anti-inflammatory treatment of asthma was studied. In vitro experiments including tension measurement and patch-clamp technique and in vivo experiments including establishment of mice model and measurement of respiratory resistance were applied to explore the role of diacerein in asthma. It turned out that agonist-precontracted mouse airway smooth muscle could be relaxed by diacerein via intracellular and extracellular calcium mobilization which was mediated by switched voltage-dependent L-type Ca2+ channels, non-selective cation channels, large-conductance Ca2+-activated K+ channel, and Na+/Ca2+ exchangers. Furthermore, diacerein could relieve bronchospasm and control airway inflammation in asthmatic mice via reduction of several inflammatory factors. Our studies elucidated the potential therapeutic property of diacerein in asthma treatment and the possible underlying mechanism. It also confirmed that new uses for already-approved drugs could be an important form of innovation.

Adoptive transfer of bone marrow-derived dendritic cells (BMDCs) alleviates OVA-induced allergic airway inflammation in asthmatic mice

Airway dendritic cells (DCs) are recognized as important factors in the mechanisms of allergic inflammatory diseases. Suppressor of cytokine signaling 3 (SOCS3) is involved in regulating the functions of T cells and macrophages, but the roles of SOCS3-expressing DCs in the pathogeneses of allergic inflammatory diseases are still controversial. We compared the effects of adoptively transferred SOCS3−/− and SOCS3+/+ bone marrow-derived DCs (BMDCs) on airway inflammation in ovalbumin (OVA)-sensitized asthmatic mice. Adoptive transfer of mature DCs (lipopolysaccharide [LPS]-induced DCs, DClps) with or without SOCS3 gene expression significantly ameliorated allergic airway inflammation. SOCS3−/− DCs slightly attenuated BMDC-induced immunogenic tolerance. DClps migrated to OVA-sensitized lungs with higher efficiency than immature DCs (DCim). DClps with or without SOCS3 greatly improved lung pathology scores and alleviated airway inflammatory cell infiltration after adoptive transfer into mice; they also increased interleukin-10 (IL-10) and transforming growth factor-β (TGF-β) production and inhibited signal transducer and activator of transcription (STAT) 4 and STAT6 signaling in the lungs after OVA sensitization. In conclusion, the BMDC adoptive transfer-induced immunogenic tolerance in OVA-sensitized mice might not be due to SOCS3 gene depletion. BMDC adoptive transfer may be developed into a new approach that alleviates asthma by modulating the balance between immune tolerance and inflammation.

Xanthatin alleviates airway inflammation in asthmatic mice by regulating the STAT3/NF-κB signaling pathway

Here, we aimed to investigate the role of Xanthatin in asthma and its underlying mechanism. BALB/c mice were treated with ovalbumin (OVA) to establis a mouse model of asthma. Our results showed that OVA injection significantly increased inflammatory cell infiltration and goblet cell hyperplasia in lung issues, while Xanthatin treatment and STAT3 inhibitor C188-9 administration relieved these symptoms. Moreover, OVA-induced OVA-specific immunoglobulin E level in serum and the number of total cell, macrophages, lymphocytes, neutrophils, and eosinophils in bronchoalveolar lavage fluid (BALF) were markedly reduced by Xanthatin treatment and signal transducer and activator of transcription 3 (STAT3) inhibition. Additionally, Xanthatin treatment and STAT3 inhibition was also significantly decreased the levels of inflammatory cytokines in BALF in asthmatic mice. We further demonstrated that the STAT3/nuclear factor-kappaB (NF-κB) pathway was blocked by Xanthatin in asthmatic mice. Overall, we conclude that Xanthatin attenuates airway inflammation in asthmatic mice through blocking the STAT3/NFκB signaling pathway, indicating the potential of Xanthatin as a useful therapeutic agent for asthma.

High-dose intranasal application of titanium dioxide nanoparticles induces the systemic uptakes and allergic airway inflammation in asthmatic mice

BackgroundTitanium dioxide nanoparticles (TiO2 NPs) have a wide range of applications in several industrial and biomedical domains. Based on the evidence, the workers exposed to inhaled nanosized TiO2 powder are more susceptible to the risks of developing respiratory diseases. Accordingly, this issue has increasingly attracted the researchers’ interest in understanding the consequences of TiO2 NPs exposure. Regarding this, the present study was conducted to analyze the local effects of TiO2 NPs on allergic airway inflammation and their uptake in a mouse model of ovalbumin (OVA)-induced allergic airway inflammation.MethodsFor the purpose of the study, female BALB/c mice with or without asthma were intranasally administered with TiO2 NPs. The mice were subjected to histological assessment, lung function testing, scanning electron microscopy (SEM), inductively coupled plasma mass spectrometry (ICP-MS), and NP uptake measurement. In addition, T helper (Th) 1/Th2 cytokines were evaluated in the lung homogenate using the enzyme-linked immunosorbent assay.ResultsAccording to the results, the mice receiving OVA alone or OVA plus TiO2 NPs showed eosinophilic infiltrates and mucus overproduction in the lung tissues, compared to the controls. Furthermore, a significant elevation was observed in the circulating Th2 cytokines, including interleukin (IL)-4, IL-5, and IL-13 after NP exposure. The TiO2 NPs were taken up by alveolar macrophages at different time points. As the results of the SEM and ICP-MS indicated, TiO2 NPs were present in most of the organs in both asthmatic and non-asthmatic mice.ConclusionBased on the findings of the current study, intranasally or inhalation exposure to high-dose nanosized TiO2 particles appears to exacerbate the allergic airway inflammation and lead to systemic uptake in extrapulmonary organs. These results indicate the very important need to investigate the upper limit of intranasally or inhalation exposure to nanosized TiO2 particles in occupational and environmental health policy.

The neuro-immune interaction in airway inflammation through TRPA1 expression in CD4+ T cells of asthmatic mice

Asthma is an inflammatory disorder of the airways dominated by a Th2-type pattern. Recently, an emerging interest arises whether transient receptor potential ankyrin 1 (TRPA1) plays a potential role in the adaptive immune response. In this study, the role of TRPA1 in the development and exacerbation of asthma was explored. The classic OVA-induced asthma and OVA plus PM2.5-induced exacerbated asthma model were used. The CD4+ T cells were sorted from spleen in asthmatic and exacerbated asthmatic mice. In the BALB/c mice treated with OVA, the increased phenotype of asthma was obtained, accompanied by the high expression of TRPA1 in lung tissue and levels of IL-4, IL-13, NGF, PGD2 in BAL. In contrast, genetic deletion or pharmacological inhibition of TRPA1 alleviated the phenotype of asthma. Similarly, in wild type (WT) C57BL/6 mice treated with OVA, the high expression of TRPA1 in lung tissues was obtained, and the levels of IL-4, IL-13, NGF, PGD2 in BAL remarkably increased when compared with those in the TRPA1 deleted mice. Furthermore, high expression of TRPA1 was detected in CD4+ T cells of OVA-treated WT C57BL/6 mice. Additional detection in the asthmatic mice exacerbated by OVA plus PM2.5 also showed high TRPA1 expression in lung tissue and CD4+ T cells. All evidence confirmed that TRPA1 is essential for the development and exacerbation of asthma. More importantly, the expression of TRPA1 in CD4+ T cells of different asthmatic mice suggested that it might be involved in neuro-immune interactions in airway inflammation of asthmatic mice.