Ovalbumin-induced Airway Inflammation Research Articles

The Clinical Translation of α-humulene - A Scoping Review.

α-humulene, a sesquiterpene found in essential oils of various plant species, has garnered interest due to its potential therapeutic applications. This scoping review aims to consolidate α-humulene's evidence base, informing clinical translation, and guiding future research directions. A scoping review was conducted of EMBASE, MEDLINE, and PubMed databases up to 14th July 2023. All studies describing original research on α-humulene extraction, as well as pre-clinical and clinical research, were included for review. Three hundred and forty articles were analysed. α-humulene yields ranged from negligible to 60.90% across plant species. In vitro experiments demonstrated cytotoxicity against adenocarcinomas (such as colorectal, pulmonary, breast, prostatic, lung, and ovarian), with varying responses in other cell models. Mechanistic insights revealed its involvement in mitochondrial dysfunction, diminished intracellular glutathione levels, and the induction of oxidative stress. In rodent studies, oral administration of α-humulene at 50 mg/kg reduced inflammation markers in paw oedema and ovalbumin-induced airway inflammation. Intraperitoneal administration of α-humulene (50 - 200 mg/kg) exhibited cannabimimetic properties through cannabinoid 1 and adenosine A2a receptors. α-humulene also exhibited a multitude of properties with potential scope for therapeutic utilisation. However, there is a paucity of studies that have successfully translated this research into clinical populations with the associated disease. Potential barriers to clinical translation were identified, including yield variability, limited isolation studies, and challenges associated with terpene bioavailability. Consequently, rigorous pharmacokinetic studies and further mechanistic investigations are warranted to effectively uncover the potential of α-humulene.

β-glucan mitigates ovalbumin-induced airway inflammation by preventing oxidative stress and CD8+ T cell infiltration

BackgroundBronchial asthma is a severe respiratory condition characterized by airway inflammation, remodeling, and oxidative stress. β-Glucan (BG) is a polysaccharide found in fungal cell walls with powerful immunomodulatory properties. This study examined and clarified the mechanisms behind BG's ameliorativeactivitiesin an allergic asthma animal model. MethodBG was extracted from Chaga mushroom and characterized using FT-IR, UV–visible, zeta potential, and 1H NMR analysis. The mice were divided into five groups, including control, untreated asthmatic, dexamethasone (Dexa)-treated (1 mg/kg), and BG (30 and 100 mg/kg)-treated groups. ResultsBG treatment reduced nasal scratching behavior, airway-infiltrating inflammatory cells, and serum levels of IgE significantly. Additionally, BG attenuated oxidative stress biomarkers by lowering malonaldehyde (MDA) concentrations and increasing the levels of reduced glutathione (GSH), glutathione peroxidase (GPx), and catalase (CAT). Immunohistochemical and flow cytometric analyses have confirmed the suppressive effect of BG on the percentage of airway-infiltrating cytotoxic CD8+ T cells. ConclusionThe findings revealed the role of CD8+ T cells in the pathogenesis of asthma and the role of BG as a potential therapeutic agent for asthma management through the suppression of airway inflammation and oxidative stress.

Expression of constitutively active TβRI leads to attenuation of ovalbumin-induced allergic airway inflammation associated with augmented M2 polarization of alveolar macrophage

BackgroundTransforming growth factor-β (Tgf-β) plays an important role in the pathogenesis of asthma through the regulation of T cells and airway epithelium. Its functions in alveolar macrophage (AM) during allergic airway inflammation remain unknown. MethodsA murine asthma model was induced with ovalbumin (ova) in TβRICA/Fsp1-Cre transgenic mice expressing constitutively active Tgf-β receptor type I (TβRICA) under the control of Fsp1-Cre transgene. Cells in the bronchoalveolar lavage (BAL) were collected to study immune cell infiltration in the lungs. Cytokine levels in BAL fluid were measured by enzyme-linked immunoassay (ELISA). Lungs were sectioned and stained with hematoxylin and eosin, periodic acid-Schiff, and trichrome for histopathologic evaluation. AMs were assessed by flow cytometry and were sorted for quantitative polymerase chain reaction analysis. ResultsOur data indicated that TβRICA transcripts were induced in AMs of TβRICA/Fsp1-Cre mice. Following the ova challenges, TβRICA/Fsp1-Cre mice exhibited reduced cellular infiltration of the airway, reduced pulmonary fibrosis, and reduced bronchial mucus secretion as compared to ova-challenged wild-type mice. An alternatively activated macrophage (M2) polarization was significantly elevated in the lungs of ova-challenged TβRICA/Fsp1-Cre mice as reflected by increased numbers of AMs expressing M2 subtype marker, CD163, in the lungs and enhanced expression of CCR2 and CD206 in AMs. Moreover, TβRICA/Fsp1-Cre AMs showed augmented expression of transcription factors, Foxo1, and IRF4, which are known to be positive regulators for M2 polarization. ConclusionsExpression of TβRICA in AMs promoted M2 polarization and ameliorated allergic airway inflammation in an ova-induced asthma mouse model.

Fallopia japonica Root Extract Ameliorates Ovalbumin-Induced Airway Inflammation in a CARAS Mouse Model by Modulating the IL-33/TSLP/NF-κB Signaling Pathway.

Fallopia japonica (Asian knotweed) is a medicinal herb traditionally used to treat inflammation, among other conditions. However, the effects of F. japonica root extract (FJE) on airway inflammation associated with combined allergic rhinitis and asthma (CARAS) and the related mechanisms have not been investigated. This study examined the effect of FJE against CARAS in an ovalbumin (OVA)-induced CARAS mouse model. Six-week-old male BALB/c mice were randomly segregated into six groups. Mice were sensitized intraperitoneally with OVA on days 1, 8, and 15, and administered saline, Dexamethasone (1.5 mg/kg), or FJE (50, 100, or 200 mg/kg) once a day for 16 days. Nasal symptoms, inflammatory cells, OVA-specific immunoglobulins, cytokine production, mast cell activation, and nasal histopathology were assessed. Administration of FJE down-regulated OVA-specific IgE and up-regulated OVA-specific IgG2a in serum. FJE reduced the production of T helper (Th) type 2 cytokines, and the Th1 cytokine levels were enhanced in nasal and bronchoalveolar lavage fluid. Moreover, FJE positively regulated allergic responses by reducing the accumulation of inflammatory cells, improving nasal and lung histopathological characteristics, and inhibiting inflammation-associated cytokines. FJE positively modulated the IL-33/TSLP/NF-B signaling pathway, which is involved in regulating inflammatory cells, immunoglobulin levels, and pro-inflammatory cytokines at the molecular level.

S14G-Humanin ameliorates ovalbumin-induced airway inflammation in asthma mediated by inhibition of toll-like receptor 4 (TLR4) expression and the nuclear factor κ-B (NF-κB)/early growth response protein-1 (Egr-1) pathway.

Asthma is a chronic inflammatory disease with a high morbidity rate in children and significantly impacts their healthy growth. It is reported that Th2 cell-mediated airway inflammation and activated oxidative stress are involved in the pathogenesis of asthma. S14G-humanin (HNG) is a derivative of Humanin with higher activity. The present study proposes to explore the potential treating property of HNG on asthma. An asthma model was constructed in mice using ovalbumin (OVA), the mice were treated with 2.5 mg/kg and 5 mg/kg HNG for 16 days. Dramatically increased lung weight index, elevated number of monocytes, eosinophils, and neutrophils, promoted production of Th2 cytokines including interleukin-4 (IL-4), interleukin-5 (IL-5), and interleukin-13 (IL-13), and severe histological pathology were observed in OVA-challenged mice, all of which were extremely alleviated by 2.5 mg/kg and 5 mg/kg HNG. Furthermore, the increased malondialdehyde (MDA) level and declined superoxide dismutase (SOD) activity in OVA-challenged mice were abolished by 2.5 mg/kg and 5 mg/kg HNG. Lastly, the upregulated TLR4, p-NF-κB p65, and early growth response 1 (Egr-1) in lung tissues of OVA-challenged mice were pronouncedly downregulated by 2.5 mg/kg and 5 mg/kg HNG. Collectively, our data suggested that HNG ameliorated airway inflammation in asthma partially due to NF-κB and Egr-1-mediated responses.

Inhaled pan-phosphodiesterase inhibitors ameliorate ovalbumin-induced airway inflammation and remodeling in murine model of allergic asthma.

Asthma is a heterogeneous, chronic respiratory disease characterized by airway inflammation and remodeling. Phosphodiesterase (PDE) inhibitors represent one of the intensively studied groups of potential anti-asthmatic agents due to their affecting both airway inflammation and remodeling. However, the effect of inhaled pan-PDE inhibitors on allergen induced asthma has not been reported to date. In this study we investigated the impact of two, representative strong pan-PDE inhibitors from the group of 7,8-disubstituted derivatives of 1,3-dimethyl-3,7-dihydro-1H-purine-2,6-dione: compound 38 and 145, on airway inflammation and remodeling in murine model of ovalbumin (OVA)-challenged allergic asthma. Female Balb/c mice were sensitized and challenged with OVA, 38 and 145 were administrated by inhalation, before each OVA challenge. The inhaled pan-PDE inhibitors markedly reduced the OVA-induced airway inflammatory cell infiltration, eosinophil recruitment, Th2 cytokine level in bronchoalveolar lavage fluid, as well as both, total and OVA-specific IgE levels in plasma. In addition, inhaled 38 and 145 decreased many typical features of airway remodeling, including goblet cell metaplasia, mucus hypersecretion, collagen overproduction and deposition, as well as Tgfb1, VEGF, and α-SMA expression in airways of allergen challenged mice. We also demonstrated that both 38 and 145 alleviate airway inflammation and remodelling by inhibition of the TGF-β/Smad signaling pathway activated in OVA-challenged mice. Taken together, these results suggest that the investigated pan-PDE inhibitors administered by inhalation are dual acting agents targeting both airway inflammation and remodeling in OVA-challenged allergic asthma and may represent promising, anti-asthmatic drug candidates.

The inhibitory effects of Bakuchicin on ovalbumin-induced allergic airway inflammation via regulating M2 macrophage polarization

Abstract Asthma is an airway inflammatory disease caused by the activation of many immune cells, including macrophages. Bakuchicin (BKC), a furanocoumarin, has anti-inflammatory properties. This study aimed to evaluate the effects of BKC on allergic airway inflammation and demonstrate the mechanisms of macrophage activation and differentiation. We assessed the effects of BKC by evaluating inflammatory markers in an ovalbumin (OVA)-induced airway inflammation mouse model and macrophage cells. BKC treatment alleviated histological changes, mast cell infiltration, and collagen deposition, and reduced the levels of myeloperoxidase, eosinophil peroxidase, β-hexosaminidase, and transforming growth factor-β in the bronchoalveolar fluid (BALF) and the level of immunoglobulins in serum. BKC ameliorated inflammatory symptoms, including the level of inducible nitric oxide synthase (iNOS) in the lung and the expression and secretion of pro-inflammatory cytokines in serum. BKC treatment reduced not only the level of Th2 cytokines but M2 macrophage marker expression and population in the BALF. In vitro, BKC inhibited LPS-stimulated production of nitric oxide and expression of pro-inflammatory cytokines through inhibition of iNOS, COX-2, Akt, MAPKs, IκBα, and NF-κB in J774 A.1 mouse macrophages. Moreover, BKC suppressed IL-4-induced M2 macrophage polarization by inhibiting arginase-1, YM-1, and Fizz-1 and regulating sirtuin 2 levels in bone marrow derived macrophages. Collectively, BKC may help in the prevention and treatment of airway inflammation by regulating macrophage activation and polarization.

Intranasal administration of Acinetobacter lwoffii in a murine model of asthma induces IL-6-mediated protection associated with cecal microbiota changes.

Early-life exposure to certain environmental bacteria including Acinetobacter lwoffii (AL) has been implicated in protection from chronic inflammatory diseases including asthma later in life. However, the underlying mechanisms at the immune-microbe interface remain largely unknown. The effects of repeated intranasal AL exposure on local and systemic innate immune responses were investigated in wild-type and Il6-/- , Il10-/- , and Il17-/- mice exposed to ovalbumin-induced allergic airway inflammation. Those investigations were expanded by microbiome analyses. To assess for AL-associated changes in gene expression, the picture arising from animal data was supplemented by in vitro experiments of macrophage and T-cell responses, yielding expression and epigenetic data. The asthma preventive effect of AL was confirmed in the lung. Repeated intranasal AL administration triggered a proinflammatory immune response particularly characterized by elevated levels of IL-6, and consequently, IL-6 induced IL-10 production in CD4+ T-cells. Both IL-6 and IL-10, but not IL-17, were required for asthma protection. AL had a profound impact on the gene regulatory landscape of CD4+ T-cells which could be largely recapitulated by recombinant IL-6. AL administration also induced marked changes in the gastrointestinal microbiome but not in the lung microbiome. By comparing the effects on the microbiota according to mouse genotype and AL-treatment status, we have identified microbial taxa that were associated with either disease protection or activity. These experiments provide a novel mechanism of Acinetobacter lwoffii-induced asthma protection operating through IL-6-mediated epigenetic activation of IL-10 production and with associated effects on the intestinal microbiome.

Fingolimod attenuates ovalbumin-induced airway inflammation via inhibiting MAPK/ERK signaling in mice.

The current study was designed to investigate the potential anti-inflammatory and antioxidant effects of fingolimod against Ovalbumin (Ova)-induced allergic airway inflammation compared to dexamethasone. Fingolimod was given (0.5 mg/kg/day, p.o.) for sensitized mice 1 hbefore Ova challenge from Days 19 to 24. Fingolimod significantly inhibited Ova-induced elevation of inflammatory cells and eosinophils numbers in bronchoalveolar lavage fluid(BALF) and reduced concentrations of immunoglobulin E in serum and of sphingosine-1-phosphate, interleukin(IL)-4, and IL-13 in BALF. Fingolimod inhibited microvascular leakage and edema as reflected by the decreased lung/body weight index. These findings were supported by histopathological examination results showing that fingolimod substantially decreased perivascular edema and inflammatory cell infiltration. Fingolimod also attenuated Ova-induced oxidative stress as evidenced by decreased malondialdehyde concentration along with increasing concentrations of reduced glutathione and superoxide dismutase in lung tissues. Fingolimod also significantly decreased monocyte chemoattractant protein-1(MCP-1), p-ERK,and p-P38 in lung tissues of Ova-challenged mice. In conclusion, the current study demonstrated the anti-inflammatory and antioxidant effects of fingolimod in allergic airway inflammation that might be associated with the downregulation of mitogen activated kinases signaling to decrease T helper 2 cytokine secretion (IL-4 and IL-13) and MCP-1 expression, along with the inhibition of oxidative stress.

The role of calcium-sensitive receptor in ovalbumin-induced airway inflammation and hyperresponsiveness in juvenile mice with asthma.

The role of the calcium-sensitive receptor (CaSR) was assessed in a juvenile mouse model of asthma induced by ovalbumin (OVA). The experiment was divided into normal control, OVA, and OVA +2.5/5mg/kg NPS2143 (a CaSR antagonist) groups. OVA induction was performed in all groups except the normal control, followed by assessing airway hyperresponsiveness (AHR) and lung pathological changes. Serum OVA-specific IgE and IgG1 were detected with an enzyme-linked immunosorbent assay (ELISA), and inflammatory cells were counted in bronchoalveolar lavage fluid (BALF). Real-time quantitative polymerase chain reaction, ELISA, and western blotting were performed to detect gene and protein expression. NPS2143 improved the OVA-induced AHR in mice, and AHR was higher in the OVA +2.5mg/kg NPS2143 group than in the OVA +5mg/kg NPS2143 group. Furthermore, NPS2143 reduced the production of OVA-specific IgE and IgG1 in serum and the number of eosinophils and lymphocytes in BALF in OVA mice with reduced CaSR expression in lung tissues. Besides, OVA-induced mice exhibited peribronchial and perivascular inflammatory cell infiltration, which was accompanied by severe goblet cell hyperplasia/hyperplasia and airway mucus hypersecretion. Furthermore, these mice exhibited increased levels of Interleukin (IL)-5, IL-13, MCP-1, and eotaxin, which were alleviated by NPS2143. The 5mg/kg NPS2143 showed more effective than the 2.5mg/kg treatment. CaSR expression was elevated in the lung tissues of OVA-induced asthmatic juvenile mice, whereas the CaSR antagonist NPS2143 reduced AHR and attenuated the inflammatory response in OVA-induced juvenile mice, possibly exerting therapeutic effects on childhood asthma.

Lactobacillus delbrueckii UFV-H2b20 increases IFN-γ production and CD39+CD73+ Treg cell numbers in lungs, and protects mice against experimental allergic asthma

Asthma is a disorder characterized by airflow obstruction, inflammation, declining airway function, bronchial hyperresponsiveness and tissue remodelling. Probiotics are defined as “live microorganisms that, when administered in adequate amounts, confer a health benefit on the host”. The use of probiotics is becoming increasingly studied and recent evidence has suggested that it may provide therapeutic benefits in asthma and other diseases. Lactobacillus delbrueckii UFV-H2b20 fulfils all the requirements to be classified as probiotic. Previous studies have already shown the ability of L. delbrueckii UFV-H2b20 to stimulate the immune system. Our objective was to evaluate the protective effects of L. delbrueckii UFV-H2b20 in experimental allergic asthma. We used a murine model of ovalbumin-induced allergic airway inflammation to mimic allergic asthma. Oral treatment with L. delbrueckii UFV-H2b20 improves respiratory parameters and inhibits the inflammatory response in the lungs by decreasing the numbers of inflammatory monocytes, eosinophils and alveolar macrophages, as well as IgE levels. Treatment increased the IFN-γ/IL-4 cytokine ratio. Levels of IL-10 in the lungs were also increased in treated animals. Our results also showed that the probiotic administration increases the number of CD39+CD73+ T regulatory lymphocytes in the lung, suggesting a role for purinergic signals in the regulation of inflammation promoted by the treatment. Understanding the mechanisms of modulation of the immune system by probiotics could allow the development of probiotic preparations that are safe and have a direct action. Our results suggest that oral administration of L. delbrueckii UFV-H2b20 could be helpful to treat chronic inflammatory airway diseases, such as asthma.

Endocannabinoid metabolism inhibition ameliorates ovalbumin-induced allergic airway inflammation and hyperreactivity in Guinea pigs

AimsEndocannabinoids are biologically active cannabinoid-related substances endogenously synthesized in many mammalian tissues. Mainly two enzymes carry out their degradation; Fatty Acid Amide Hydrolase (FAAH) and Monoacylglycerol Lipase (MAGL). Endocannabinoids are shown to affect the modulation of inflammatory processes and airway responsiveness. In the present study, we investigated the effects of FAAH and MAGL inhibitor treatments in experimental allergic airway inflammation in guinea pigs. Materials and methodsGuinea pigs were sensitized and challenged by ovalbumin to induce an allergic asthma model. Then, the effects of FAAH inhibitor URB597, MAGL inhibitor JZL184, and dual (FAAH/MAGL) inhibitor JZL195 on airway inflammation and hyperreactivity were evaluated. Key findingsOvalbumin challenge increased airway reactivity, IgE in serum, IL-4, and IL-13, and the percentage of eosinophils in bronchoalveolar lavage (BAL). In addition, inhibition of FAAH or MAGL enzymes leads to an increase in endocannabinoid levels. The selective inhibition of the FAAH enzyme prevented inflammation indicators such as cytokine production and inflammatory cell infiltration but had a negligible effect on airway hyperreactivity. However, the inhibition of the MAGL enzyme or dual inhibition of both FAAH and MAGL enzymes tent to moderate both pulmonary inflammation and airway hyperreactivity. SignificanceWe have previously demonstrated that modulation of endocannabinoid levels in the airways by FAAH or MAGL inhibition can be useful in preventing acute lung inflammation. The results of the present study further suggest that FAAH and MAGL inhibitor treatment can also be a promising strategy for bronchial hyperreactivity and airway inflammation in allergic asthma.

Co-exposure of peptidoglycan and heat-inactivated Asian sand dust exacerbates ovalbumin-induced allergic airway inflammation in mice

Aims Asian sand dust (ASD) comprises soil particles, microorganisms, and various chemical components. We examined whether peptidoglycan (PGN), a structural cell wall component of Gram-positive bacteria, exacerbates ASD-induced allergic airway inflammation in mice. Methods The ASD (median diameter ∼4 µm) used was a certified reference material from the National Institute for Environmental Studies in Japan, derived from Gobi Desert surface soil collected in 2011. BALB/c mice were intratracheally exposed to PGN, heat-inactivated ASD (H-ASD), and ovalbumin (OVA), individually and in combination. Twenty-four hours after the final intratracheal administration, bronchoalveolar lavage fluid (BALF) and serum samples were collected. Inflammatory cell count, cytokine levels in the BALF, OVA-specific immunoglobulin levels in the serum, and pathological changes in the lungs were analyzed. Results and Discussion After OVA + PGN + H-ASD treatment, the number of eosinophils, neutrophils, and macrophages in the BALF and of eosinophils in the lung tissue was significantly higher than that after OVA + PGN or OVA + H-ASD treatment. Moreover, levels of chemokines and cytokines associated with eosinophil recruitment and activation were significantly higher in the BALF of this group than in that of the OVA + PGN group, and tended to be higher than those in the OVA + H-ASD group. Pathological changes in the lungs were most severe in mice treated with OVA + PGN + H-ASD. Conclusions Our results indicate that PGN is involved in the exacerbation of ASD-induced allergic airway inflammation in mice. Thus, inhalation of ASD containing Gram-positive bacteria may trigger allergic bronchial asthma.

Reaction of eosinophilic granulocytes of guinea pigs airways to the experimental allergic inflammation according to the morphometric study

Background. After creating an animal model of experimental airways allergic inflammation using ovalbumin, scientists mainly studied the reaction of the cellular and humoral links of the acquired specific immunity. At the same time, it is known that the development of allergic inflammation of the airways to the effect of the environmental chemoattractants is primarily the result of the local innate immune system response. Pulmonary neuroendocrine cells of the airway epithelium with the help of neuropeptides activate the secretion of IL-5 and IL-13 by type 2 innate lymphoid cells IL-5 determines the eosinophilic inflammation. The question of the reaction of the components of innate immunity of the respiratory tract to the allergic inflammation in most aspects remains open. open. Objective. The purpose of the current study was to define the reaction of eosinophilic granulocytes in guinea pigs lungs as an important component of the innate immunity of the respiratory tract to experimental ovalbumin-induced allergic inflammation according to the data of a morphometric study. Methods. Histological, morphometric, statistical methods were used to study the topographic features and the number of eosinophils in the lungs of male 48 guinea pigs on the 23rd, 30th, 36th and 44th days after initiation of the experimental ovalbumin-induced allergic airway inflammation. Results. Our study demonstrates a significant reaction occurs on the part of the cellular link of innate immunity, which consists in the activation of eosinophils, in the experimental model of ovalbumin-induced airways allergic inflammation. The most significant changes were observed in the distal parts of the intrapulmonary airways and in the structures of the pulmonary acinus in the early period of the development of the inflammatory process (23rd and 30th days after the start of the experiment). The late (36th and 44th days after the start of the experiment) period of the development of an allergic inflammatory process in the lungs is accompanied by a gradual decrease in the activity of eosinophilic inflammation. At the same time, the quantitative indicators remain statistically significantly higher in the intact and control groups, which indicates the continuation of allergic inflammation in the absence of the action of the allergen and is a manifestation of the violation of the recovery and adaptation processes in the local immune system of the lung. Conclusion. After ovalbumin-sensitization and aeroallergization eosinophilic inflammation develops in the lungs of a guinea pig, as a result of the reaction of the innate immunity to the action of an allergen. Actively and first of all, allergic eosinophilic inflammation develops in the distal airways (terminal bronchioles) and in the connective tissue stroma of the pulmonary acinus.

Lipoxin A4 inhibits ovalbumin-induced airway inflammation and airway remodeling in a mouse model of asthma

Asthma is a chronic respiratory disease, which is characterized by airway inflammation, remodeling and airway hyperresponsiveness. Airway remodeling is caused by long-term inflammation of the airways. Lipoxin A4 (LXA4) is a natural eicosanoid with powerful anti-inflammatory properties, and has been shown to serve a critical role in orchestrating pulmonary inflammation and airway hyper-responsiveness in asthmatic mice. However, its effect on airway remodeling is unknown. Female BALB/c mice were used to establish a mouse model of asthma which were sensitized and challenged by ovalbumin (OVA). LXA4 was intranasally administrated prior to the challenge. The results of our study indicated that LXA4 suppressed the OVA-induced inflammatory cell infiltration and T helper type 2 (Th2) cytokines secretion in the mouse model of asthma. Characteristics of airway remodeling, such as thickening of the bronchial wall and smooth muscle, overdeposition of collagen, and overexpression of α-smooth muscle actin (α-SMA) and collagen-I were reversed by LXA4. Furthermore, LXA4 suppressed the aberrant activation of the signal transducer and activator of transcription 3 (STAT3) pathway in the lung tissues of asthmatic mice. In conclusion, these findings demonstrated that LXA4 alleviated allergic airway inflammation and remodeling in asthmatic mice, which may be related to the inhibition of STAT3 pathway.

IgE cross-linking induces activation of human and mouse mast cell progenitors

The concept of innate and adaptive effector cells that are repleted by maturing inert progenitor cell populations is changing. Mast cells develop from rare mast cell progenitors populating peripheral tissues at homeostatic conditions, or as a result of induced recruitment during inflammatory conditions. Because FcεRI-expressing mast cell progenitors are the dominating mast cell type during acute allergic lung inflammation invivo, we hypothesized that they are activated by IgE cross-linking. Mouse peritoneal and human peripheral blood cells were sensitized and stimulated with antigen, or stimulated with anti-IgE, and the mast cell progenitor population analyzed for signs of activation by flow cytometry. Isolated peritoneal mast cell progenitors were studied before and after anti-IgE stimulation at single-cell level by time-lapse fluorescence microscopy. Lung mast cell progenitors were analyzed for their ability to produce IL-13 by intracellular flow cytometry in a mouse model of ovalbumin-induced allergic airway inflammation. Sensitized mouse peritoneal mast cell progenitors demonstrate increased levels of phosphorylation of tyrosines on intracellular proteins (total tyrosine phosphorylation), and spleen tyrosine kinase (Syk) phosphorylation after antigen exposure. Anti-IgE induced cell surface-associated lysomal-associated membrane protein-1 (LAMP-1) in naive mast cell progenitors, and prompted loss of fluorescence signal and altered morphology of isolated cells loaded with lysotracker. In human mast cell progenitors, anti-IgE increased total tyrosine phosphorylation, cell surface-associated LAMP-1, and CD63. Lung mast cell progenitors from mice with ovalbumin-induced allergic airway inflammation produce IL-13. Mast cell progenitors become activated by IgE cross-linking and may contribute to the pathology associated with acute allergic airway inflammation.

Vitamin D Supplementation: Oxidative Stress Modulation in a Mouse Model of Ovalbumin-Induced Acute Asthmatic Airway Inflammation.

Asthma oxidative stress disturbances seem to enable supplementary proinflammatory pathways, thus contributing to disease development and severity. The current study analyzed the impact of two types of oral vitamin D (VD) supplementation regimens on the redox balance using a murine model of acute ovalbumin-induced (OVA-induced) asthmatic inflammation. The experimental prevention group received a long-term daily dose of 50 µg/kg (total dose of 1300 µg/kg), whereas the rescue group underwent a short-term daily dose of 100 µg/kg (total dose of 400 µg/kg). The following oxidative stress parameters were analyzed in serum, bronchoalveolar lavage fluid (BALF) and lung tissue homogenate (LTH): total oxidative status, total antioxidant response, oxidative stress index, malondialdehyde and total thiols. Results showed that VD significantly reduced oxidative forces and increased the antioxidant capacity in the serum and LTH of treated mice. There was no statistically significant difference between the two types of VD supplementation. VD also exhibited an anti-inflammatory effect in all treated mice, reducing nitric oxide formation in serum and the expression of nuclear factor kappa B p65 in the lung. In conclusion, VD supplementation seems to exhibit a protective role in oxidative stress processes related to OVA-induced acute airway inflammation.

Atractylodin attenuates the expression of MUC5AC and extracellular matrix in lipopolysaccharide-induced airway inflammation by inhibiting the NF-κB pathway.

This study aimed to explore the effects of atractylodin (ATR) on lipopolysaccharide (LPS)-induced inflammatory response in human airway epithelial cells. The cytotoxicity was assessed by CCK-8 assay. The mRNA expression and concentration of interleukin (IL)-6, IL-8, and mucin 5AC (MUC5AC) were measured by qRT-PCR and ELISA, respectively. Western blotting was performed to determine protein expression. We found that LPS stimulation increased the mRNA expression and concentrations of IL-6, IL-8, and MUC5AC, as well as the expression of Col-I and FN in 16HBE cells, but this effect of LPS was attenuated by ATR treatment. Mechanistically, ATR suppressed LPS-induced activation of the NF-κB pathway in 16HBE cells. Moreover, ATR repressed ovalbumin-induced airway inflammation and NF-kB pathway in mice. In conclusion, ATR attenuated the expression of MUC5AC and ECM in LPS-induced airway inflammation by inhibiting the NF-κB pathway.

Ovalbumin-Induced Airway Inflammation Is Ameliorated in Dectin-1-Deficient Mice, in Which Pulmonary Regulatory T Cells Are Expanded through Modification of Intestinal Commensal Bacteria.

Asthma is an allergic chronic respiratory disease that affects more than 300 million people around the world. Dysbiosis of intestinal commensal microbiota influences the development of asthma. Dectin-1 (gene symbol: Clec7a), a C-type lectin receptor, plays an important role in the intestinal immune homeostasis by controlling regulatory T (Treg) cell differentiation through regulation of intestinal microbiota. However, it is not clear whether intestinal immune conditions affect immune responses in other organs. In this study, we examined the effects of Dectin-1 deficiency on allergic airway inflammation (AAI). OVA-induced AAI was attenuated in Clec7a -/- mice. Treg cells were more abundant in colonic lamina propria, mesenteric lymph nodes, and bronchoalveolar lavage fluid of Clec7a -/- mice after AAI induction. Treatment with antibiotics, but not an antifungal agent, decreased the abundance of intestinal Treg cells and aggravated the symptoms of AAI in Clec7a -/- mice. Transplantation of gut microbiota from Clec7a -/- mice into antibiotic-treated hosts increased the abundance of intestinal Treg cells and ameliorated AAI. Overcolonization by Lactobacillus murinus, a Dectin-1 signaling-regulated commensal bacterium, also promoted expansion of Treg cells in the colon and suppressed lung inflammation. Depletion of Treg cells with anti-CD25 Ab eliminated the phenotypic differences between wild-type and Clec7a -/- mice in OVA-induced AAI. These observations suggest that inhibition of Dectin-1 signaling ameliorates AAI by increasing the abundance of Treg cells in lungs through modification of intestinal commensal bacteria, suggesting a role for commensal microbiota in regulating inflammation in organs other than the intestine.

Cryptotympana pustulata Extract and Its Main Active Component, Oleic Acid, Inhibit Ovalbumin-Induced Allergic Airway Inflammation through Inhibition of Th2/GATA-3 and Interleukin-17/RORγt Signaling Pathways in Asthmatic Mice.

Cicadae Periostracum (CP), derived from the slough of Cryptotympana pustulata, has been used as traditional medicine in Korea and China because of its diaphoretic, antipyretic, anti-inflammatory, antioxidant, and antianaphylactic activities. The major bioactive compounds include oleic acid (OA), palmitic acid, and linoleic acid. However, the precise therapeutic mechanisms underlying its action in asthma remain unclear. The objective of this study was to determine the antiasthmatic effects of CP in an ovalbumin (OVA)-induced asthmatic mouse model. CP and OA inhibited the inflammatory cell infiltration, airway hyperresponsiveness (AHR), and production of interleukin (IL)7 and Th2 cytokines (IL-5) in the bronchoalveolar lavage fluid and OVA-specific imunoglobin E (IgE) in the serum. The gene expression of IL-5, IL-13, CCR3, MUC5AC, and COX-2 was attenuated in lung tissues. CP and OA might inhibit the nuclear translocation of GATA-binding protein 3 (GATA-3) and retinoic acid receptor-related orphan receptor γt (RORγt) via the upregulation of forkhead box p3 (Foxp3), thereby preventing the activation of GATA-3 and RORγt. In the in vitro experiment, a similar result was observed for Th2 and GATA-3. These results suggest that CP has the potential for the treatment of asthma via the inhibition of the GATA-3/Th2 and IL-17/RORγt signaling pathways.