Idiopathic pulmonary fibrosis (IPF) and lung cancer (LC) constitute two progressively devastating lung diseases with common risk factors including aging and smoking. There is an increasing interest in the investigation of common pathogenic mechanisms between IPF and LC with therapeutic implications. Several oncomirs, microRNAs associated with malignancy, are also linked with IPF. miR‑29a and miR‑185 downregulation is probably involved both in carcinogenesis and fibrogenesis. We have previously observed miR‑29a and miR‑185 downregulation in IPF cells from bronchoalveolar lavage (BAL) and in this study we investigated their expression in LC BAL cells. Common targets of miR‑29a and miR‑185 such as DNA methyltransferase (DNMT)1, DNMT3b, COL1A1, AKT1 and AKT2 were measured. Potential correlations with pulmonary function tests, smoking status and endobronchial findings were investigated. Similar levels of miR‑29a and miR‑185 were detected in IPF and LC while their common targets AKT1 and DNMT3b were not found to differ, suggesting potential pathogenetic similarities at the level of key epigenetic regulators. By conrast, COL1A1 mRNA levels were increased in IPF suggesting a disease‑specific mRNA signature. Notably, DNMT1 was downregulated in the LC group and its expression was further reduced in the presence of increasing malignant burden as it was implied by the endobronchial findings.

Asthma is a common chronic inflammatory respiratory disease characterised by airway inflammation and hyperresponsiveness. The present study was designed to clarify the effect of intranasal miR‑410 administration in an ovalbumin (OVA)‑induced murine model of asthma. It was found that miR‑410 expression was significantly decreased in the lungs of OVA‑induced asthmatic mice (P<0.05) and miR‑410 was overexpressed via intranasal instillation. Bioinformatics indicated that the 3'‑untranslated regions of interleukin (IL)‑4 and IL‑13 messenger RNAs (mRNAs) contain miR‑410 binding sites. The IL‑4 and IL‑13 genes were confirmed to be miR‑410‑regulated using the dual‑luciferase reporter assay. Additionally, intranasal administration of miR‑410 markedly attenuated airway inflammation and reduced infiltration of inflammatory cells into bronchoalveolar lavage fluid (P<0.05) as determined by bronchoalveolar lavage fluid analysis. Moreover, miR‑410 significantly decreased the lung expression of IL‑4 and IL‑13 (P<0.05), although the levels of mRNAs encoding IL‑4 and IL‑13 in lungs did not change significantly as determined by real‑time PCR analysis. In conclusion, we found that intranasal administration of miR‑410 effectively inhibited airway inflammation in OVA‑induced asthmatic mice by targeting IL‑4 and IL‑13 at the post‑transcriptional level. miR‑410 is thus a promising treatment for allergic asthma.

Dexmedetomidine (DEX) suppresses inflammatory responses and protects against organ injury. The aim of the present study was to investigate the effect of DEX on airway hyperresponsiveness (AHR) and allergic airway inflammation, as well as its underlying mechanism of action in a murine model of ovalbumin (OVA)‑induced asthma. A total of 30 female BALB/c mice were divided into 6 groups (n=5 mice/group): Control, OVA, OVA + DEX (20, 30 or 50 µg/kg) and OVA + TAK‑242 [a toll‑like receptor 4 (TLR4) inhibitor]. The mice were intraperitoneally injected with 20, 30 or 50 µg/kg DEX 1 h before OVA challenge. AHR to inhaled methacholine (Mch) was measured, and the mice were sacrificed 24 h after the last challenge. AHR following Mch inhalation was measured using the FlexiVent apparatus. Hematoxylin and eosin, periodic acid‑Schiff and Wright‑Giemsa staining was performed to evaluate inflammatory cell infiltration in the lung tissue. The levels of IL‑4, IL‑5 and IL‑13 in the bronchoalveolar lavage fluid were analyzed using ELISA, and their mRNA expression levels in the lung tissue were examined using reverse transcription‑quantitative PCR. The protein expression of TLR4, NF‑κB and phosphorylated (p)NF‑κB in the lung tissue was also detected using immunohistochemistry. In the murine OVA‑induced asthma model, DEX decreased AHR following Mch inhalation and reduced the infiltration of inflammatory cells. IL‑4, IL‑5 and IL‑13 levels in the bronchoalveolar lavage fluid were significantly lower following DEX treatment. Furthermore, DEX treatment inhibited the expression of TLR4, NF‑κB and p‑NF‑κB in the lung tissue and exhibited a similar effect to TAK‑242 treatment. In conclusion, DEX may attenuate AHR and allergic airway inflammation by inhibiting the TLR4/NF‑κB pathway. These results suggested that DEX may represent a potential anti‑inflammatory agent for the treatment and management of patients with asthma.

Idiopathic pulmonary fibrosis is a chronic and progressive fibrotic lung disorder with unknown etiology and a high mortality rate. Tanshinone ⅡA (Tan ⅡA) is a lipophilic diterpene extracted from the Chinese herb Salvia miltiorrhiza Bunge with diverse biological functions. The present study was conducted to evaluate the effects of Tan ⅡA on bleomycin (BLM)‑induced pulmonary fibrosis in rats. Rats received an intraperitoneal injection of Tan ⅡA and normal rats were used as controls. Severe pulmonary edema, inflammation and fibrosis were observed in the BLM‑treated rats and the counts of total cells, neutrophils and lymphocytes were significantly increased in the bronchoalveolar lavage fluids of those rats. These pathological changes were markedly attenuated by subsequent treatment with Tan ⅡA. In addition, BLM‑induced increased expression of tumor necrosis factor‑α, interleukin (IL)‑1β, IL‑6, cyclooxygenase‑2, prostaglandin E2, malondialdehyde, inducible nitric oxide synthase and nitric oxide in rats, which was also suppressed by Tan ⅡA injection. The present findings suggest therapeutic potential of Tan ⅡA for pulmonary fibrosis.

Acute lung injury (ALI) is a complex condition frequently encountered in the clinical setting. The aim of the present study was to investigate the effect of conditioned media (CM) from human adipose‑derived mesenchymal stromal cells (MSCs) activated by flagellin (F‑CM), a Toll‑like receptor 5 ligand, on inflammation‑induced lung injury. In the in vitro study, RAW264.7 macrophages treated with F‑CM had a higher proportion of cells with the M2 phenotype, lower expression of pro‑inflammatory factors and stronger expression of anti‑inflammatory genes compared with the CM from normal adipose‑derived MSCs. Furthermore, in vivo experiments were performed in mice with ALI induced by intraperitoneal injection of lipopolysaccharide. F‑CM significantly alleviated the lung exudation, inhibited inflammatory cell recruitment in lung tissues and decreased the concentration of inflammatory factors in the bronchoalveolar lavage fluid. These findings indicated that F‑CM has superior anti‑inflammation ability compared with CM, and that it may represent a promising therapeutic approach to the treatment of inflammation‑induced ALI.

Sirtuin (SIRT)3 is closely related to inflammation and apoptosis and studies have described this relationship, including in the lungs. However, the expression of SIRT3 and its effect on apoptosis and inflammation in bronchial tissue in asthma remains to be elucidated. The present study found that SIRT3 expression decreased in the bronchial tissues of asthmatic mice and its upregulation could not only reduce increased bronchial epithelial cells apoptosis in the asthmatic mice but also significantly decreased the elevated expression of cytokines (TNF‑α, IL‑4, IL‑5 and IL‑13) in bronchoalveolar lavage fluid. Further study found that SIRT3 overexpression significantly decreased apoptosis‑related protein expression (Bax/Bcl2 ratio and caspase 3 activity) and oxidative injury. In vitro, SIRT3 regulated oxidative stress‑induced bronchial epithelial cell (16HBE) apoptosis and cytokine expression. In conclusion, SIRT3 expression decreased in bronchial tissues of asthmatic mice and the upregulation of SIRT3 expression could reduce the apoptosis of bronchial epithelium and airway inflammation. It was concluded that SIRT3 might be a potential target in asthma treatment.

The present study aimed to investigate the effect of epigallocatechin gallate (EGCG) on airway inflammation in mice with bronchial asthma, and the regulatory mechanism of transforming growth factor (TGF)‑β1 signaling pathway, so as to provide theoretical basis for research and development of a novel drug for clinical treatment. Mouse models of bronchial asthma were established and injected with dexamethasone and EGCG via the caudal vein. 7 days later, bronchoalveolar tissue was collected for hematoxylin and eosin staining. Determination of airway resistance (AWR) and lung function in mice was detected. Serum was separated for cytometric bead array to detect the changes in inflammatory factors. Bronchoalveolar lavage fluid was collected for eosinophil and neutrophil counts. Fresh blood was obtained for flow cytometry to determine the percentages of Th17 and Treg cells. Bronchovesicular tissue was utilized for western blot assay and reverse transcription‑quantitative polymerase chain reaction to determine the proteins and transcription factors in the TGF‑β1 pathway. EGCG 20 mg/kg significantly reduced asthmatic symptoms, lung inflammatory cell infiltration, and the inflammatory factor levels of interleukin (IL)‑2, IL‑6 and tumor necrosis factor (TNF)‑α. In addition, it increased the levels of inflammatory factors, including IL‑10, diminished the percentage of Th17 cells, increased the percentage of Treg cells, and decreased the expression of TGF‑β1 and phosphorylated (p)‑Smad2/3 expression. Following the inhibition of the TGF‑β1 receptor, the anti‑inflammatory effect of EGCG disappeared, and the expression of TGF‑β1 and p‑Smad2/3 increased. EGCG attenuated airway inflammation in asthmatic mice, decreased the percentage of Th17 cells and increased the percentage of Treg cells. The anti‑inflammatory effect of EGCG is achieved via the TGF‑β1 signaling pathway.

Neutrophil gelatinase‑associated lipocalin (NGAL) is a 25‑kDa protein of the lipocalin superfamily and its presence was initially observed in activated neutrophils. It has previously been demonstrated that the expression of NGAL is markedly increased in stimulated epithelia, and is important in the innate immunological response to various pathophysiological conditions, including infection, cancer, inflammation and kidney injury. The present study constructed a ventilator‑associated lung injury model in mice. NGAL mRNA and protein expression levels in lung tissue were detected using reverse transcription‑quantitative polymerase chain reaction and western blotting, respectively. In addition, NGAL protein levels in bronchoalveolar lavage fluid and serum were measured via western blotting. The results of the present study suggested that NGAL expression increased under all mechanical ventilation treatments. The increase was most prominent in the high peak inflation pressure and high‑volume mechanical ventilation groups, where there was the greatest extent of lung injury. In addition, NGAL expression increased in a time‑dependent manner under high‑volume mechanical ventilation, consistent with the degree of lung injury. These findings suggested that NGAL may serve as a potential novel biomarker in ventilator‑associated lung injury.

Sirtuin 1 (SIRT1) is involved in the pathogenesis of allergic asthma. This study aimed to investigate whether EX‑527, a specific SIRT1 inhibitor, exerted suppressive effects on allergic airway inflammation in mice submitted to ovalbumin (OVA) inhalation. In addition, this study assessed whether such a protective role was mediated by autophagy suppression though mammalian target of rapamycin (mTOR) activation. Female C57BL/6 mice were sensitized to OVA and EX‑527 (10 mg/kg) was administered prior to OVA challenge. The study found that EX‑527 reversed OVA‑induced airway inflammation, and reduced OVA‑induced increases in inflammatory cytokine expression, and total cell and eosinophil counts in bronchoalveolar lavage fluid. In addition, EX‑527 enhanced mTOR activation, thereby suppressing autophagy in allergic mice. To assess whether EX‑527 inhibited airway inflammation in asthma through the mTOR‑mediated autophagy pathway, rapamycin was administered to mice treated with EX‑527 after OVA sensitization. All effects induced by EX‑527, including increased phosphorylated‑mTOR and decreased autophagy, were abrogated by rapamycin treatment. Taken together, the present findings indicated that EX‑527 may inhibit allergic airway inflammation by suppressing autophagy, an effect mediated by mTOR activation in allergic mice.

Acute lung injury (ALI) is a severe lung syndrome with high morbidity and mortality, due to its complex mechanism and lack of effective therapy. The use of placenta‑derived mesenchymal stem cells (pMSCs) has provided novel insight into treatment options of ALI. The effects of pMSCs on lipopolysaccharide (LPS)‑induced inflammation were studied using a co‑culture protocol with LPS‑stimulated RAW264.7 cells. An LPS‑induced ALI Sprague‑Dawley rat model was developed by intravenously injecting 7.5 mg/kg LPS, and intratracheal instillation of 1x105 pMSCs was performed after administration of LPS to investigate the therapeutic potential of these cells. pMSCs ameliorated LPS‑induced ALI, as suggested by downregulated pro‑inflammatory cytokine tumor necrosis factor‑α and increased anti‑inflammatory cytokine interleukin‑10 in both cell and animal models. Moreover, the protein and leukocyte cells in bronchoalveolar lavage fluid decreased at a rapid rate after treatment with pMSCs. Histopathology demonstrated that pMSCs alleviated the infiltration of inflammatory cells, pulmonary hyperemia and hemorrhage, and interstitial edema. In addition, pMSC reduced the LPS‑induced expression of C‑X‑C motif chemokine ligand 12 in RAW264.7 macrophages and in lung tissue of ALI rats. This demonstrated that pMSCs are therapeutically effective in LPS‑induced ALI.

Acute lung injury (ALI) is characterized by tissue damage and inflammatory cytokine secretion; however, the therapeutic options available to treat ALI remain limited. Necrostatin‑1 (Nec‑1) has the ability to attenuate cell necroptosis in various inflammatory diseases. The present study evaluated the protective effects of Nec‑1 on a mouse model of lipopolysaccharide‑induced ALI. Histological alterations in the lungs were evaluated through hematoxylin and eosin staining, and the expression levels of cytokines in the bronchoalveolar lavage fluid and lung tissues were determined by ELISA. In addition, accumulated production of reactive oxygen species was determined by staining with DCFH‑DA probes, western blotting and immunofluorescence. The results revealed that treatment with the necroptosis inhibitor, Nec‑1, exerted significant protective effects on ALI‑induced inflammation and necroptosis. The key proteins involved in necroptosis were markedly reduced, including receptor‑interacting serine/threonine‑protein kinase (RIP)1 and RIP3. Notably, antioxidant proteins were upregulated by Nec‑1, which may attenuate oxidative stress. Furthermore, treatment with Nec‑1 markedly suppressed necroptosis in the pulmonary alveoli RLE‑6TN cell line. Taken together, these data revealed a novel association between ALI and necroptosis, and suggested that necroptosis inhibitors may be used as effective anti‑inflammatory drugs to treat ALI.

Changes in pulmonary microvascular permeability following cardiopulmonary bypass (CPB) and the underlying mechanisms have not yet been established. Therefore, the aim of the present study was to elucidate the alterations in pulmonary microvascular permeability following CPB and the underlying mechanism. The pulmonary microvascular permeability was measured using Evans Blue dye (EBD) exclusion, and the neutrophil infiltration and proinflammatory cytokine secretion was investigated. In addition, the activation of Src kinase and the phosphorylation of caveolin‑1 and vascular endothelial cadherin (VE‑cadherin) was examined. The results revealed that CPB increased pulmonary microvascular leakage, neutrophil count and proinflammatory cytokines in the bronchoalveolar lavage fluid, and activated Src kinase. The administration of PP2, an inhibitor of Src kinase, decreased the activation of Src kinase and attenuated the increase in pulmonary microvascular permeability observed following CPB. Two important proteins associated with vascular permeability, caveolin‑1 and VE‑cadherin, were significantly activated at 24 h in the lung tissues following CPB, which correlated with the alterations in pulmonary microvascular permeability and Src kinase. PP2 administration inhibited their activation, suggesting that they are downstream factors of Src kinase activation. The data indicated that the Src kinase pathway increased pulmonary microvascular permeability following CPB, and the activation of caveolin‑1 and VE‑cadherin may be involved. Inhibition of this pathway may provide a potential therapy for acute lung injury following cardiac surgery.

The aim of the present study was to examine the role of Wnt signaling in lipopolysaccharide (LPS)‑induced acute respiratory distress syndrome (ARDS). ARDS was induced by LPS and compared in mice treated with either glycogen synthase kinase‑3β inhibitor (GSKI) or PBS. The protein expression levels of interleukin (IL)‑6, IL‑8, tumor necrosis factor (TNF)‑α, IL‑17, IL‑18 and IL‑1β in the bronchoalveolar lavage fluid (BALF) were examined using murine cytokine‑specific enzyme‑linked immunosorbent assays. The accumulation of neutrophils and macrophages in the BALF were detected using flow cytometry. The extent of pathological lesions was evaluated using an immunohistochemical assay. The differentiation of mesenchymal stem cells (MSCs) into type II alveolar (ATII) epithelial cells was analyzed using immunofluorescence staining. Treatment with GSKI led to maintained body weights and survival in mice with LPS‑induced ARDS. Treatment with GSKI effectively reduced the levels of total protein, albumin, IgM and keratinocyte growth factor in the BALF. Smith scores showed that GSKI significantly alleviated LPS‑induced lung injury. GSKI also functioned to reduce inflammatory cell accumulation and pro‑inflammatory cytokine secretion. Finally, it was found that GSKI promoted the differentiation of MSCs into ATII epithelial cells in vivo. Taken together, the GSKI‑treated mice exhibited reduced acute lung injury through inhibited intra‑fluid inflammatory cell infiltration and decreased expression of pro‑inflammatory cytokines, and GSKI increased the differentiation of MSCs into ATII epithelial cells.

The present study was designed to investigate the effects of liver soothing pingchuan formula decoction (LSPF) on experimental asthma in BALB/c mice and explore its potential molecular mechanisms. An animal model of asthma was established in BALB/c mice through sensitization and activation with intraperitoneal injection of 10% ovalbumin (OVA)/Al(OH)3 solution in addition to inhalation of a 5% OVA solution. LSPF (300 and 600 mg/kg/day) was initially administered orally prior to activation. Following this, bronchoalveolar lavage fluid (BALF) and lung tissues were collected for histopathalogical examination. Levels of inflammatory cells and cytokines were determined in the BALF, and levels of nerve growth factor (NGF) and tyrosine kinase A (TrkA) in the lung tissues were determined. The results of the present study indicated that increased inflammatory reactions were observed following OVA sensitization (P<0.05), and the expression levels of NGF (P<0.05) and TrkA (P<0.05) were significantly increased, compared with normal mice. Notably, compared with the asthma model group, immunohistochemical results revealed that LSPF treatment suppressed OVA induced inflammatory reactions (P<0.05) and NGF (P<0.05) and TrkA expression levels (P<0.05). In addition, the NGF (P<0.05) and TrkA (P<0.05) were revealed to be downregulated with LSPF treatment from the results of the ELISA and western blotting assay. Overall, the results of the present study demonstrated that LSPF exhibits therapeutic effects on experimental asthma in mice, via downregulation of the NGF-TrkA pathway.

Oridonin is an extract obtained from a traditional Chinese medicinal herb, Xihuangcao. Previous studies have demonstrated that Oridonin exerts various pharmaceutical effects, such as anti‑tumor and immunosuppressive effects, as well as modulating cytokine balance. The present study identified that Oridonin could regulate the Th1/Th2 cytokine balance in mice. However, as the anti‑asthmatic effect of Oridonin is currently unknown a mouse model of asthma was used in the present study. BALB/c mice were sensitized using ovalbumin (OVA), then the sensitized mice were treated with Oridonin prior to OVA challenge. The in vivo study indicated that Oridonin decreased the OVA‑induced airway hyper‑responsiveness significantly (P<0.05). In addition, the results indicated that in Oridonin‑treated mice, the eosinophil number and total inflammatory cell number in bronchoalveolar lavage (BAL) fluid decreased significantly in the Oridonin group when compared with the control group. Further study indicated that Oridonin significantly decreased the level of inflammatory cytokines, which were induced by OVA, in BAL fluid. Histological studies were performed to evaluate the effect of Oridonin on eosinophilia and mucus in the airway, the results indicated that Oridonin significantly inhibited the eosinophilia and mucus production in the lungs. Therefore the present study demonstrated that Oridonin regulates Th1/Th2 balance in mice and exhibited anti‑asthmatic effects in a mouse model of asthma. These findings indicate that Oridonin may serve as a potential therapeutic compound for the treatment of asthma in future.

Neutrophilic asthma (NA) is characterized by neutrophil‑mediated inflammation and the presence of Th17 cells. However, the mechanisms underlying Th17 cell responses in NA remain unknown. The aim of the present study was to examine the effects of interleukin (IL)‑7 on Th17 cell responses in NA. A NA mouse model was sensitized by airway delivery of ovalbumin (OVA) and lipopolysaccharide and challenged with 1% OVA aerosol from day 21 for 3 consecutive days. Airway resistance was then measured to assess airway hyper‑responsiveness (AHR). Cells from bronchoalveolar lavage fluid (BALF) underwent Diff‑Quick and hematoxylin and eosin staining for classification. The levels of IL‑17 in the BALF were determined by ELISA. The effects of IL‑7 administration and STAT5 inhibition on Th17 cells were also characterized in vitro using splenic CD4+ T cells. Ki‑67, Bcl‑2 and activated caspase‑3 expression in differentiated Th17 cells were analyzed by flow cytometry. The mouse model of NA was characterized by increased AHR, elevated levels of IL‑17, high neutrophil counts in BALF, accumulated inflammatory cells in the lung and Th17 cell responses. IL‑7 promoted the expression of Ki‑67 and Bcl‑2 while reducing caspase‑3 expression. STAT5 inhibitor treatment decreased the levels of Ki‑67 and Bcl‑2, and resulted in increased expression of caspase‑3. These results suggested that the IL‑7/JAK/STAT5 signaling pathway may be involved in Th17 cell responses in NA.

Mechanical ventilation (MV) can contribute to ventilator‑induced lung injury (VILI); dexmedetomidine (Dex) treatment attenuates MV‑related pulmonary inflammation, but the mechanisms remain unclear. Therefore, the present study aimed to explore the protective effect and the possible molecular mechanisms of Dex in a VILI rodent model. Adult male Sprague‑Dawley rats were randomly assigned to one of seven groups (n=24 rats/group). Rats were euthanized after 4 h of continuous MV, and pathological changes, lung wet/dry (W/D) weight ratio, the levels of inflammatory cytokines (IL‑1β, TNF‑α and IL‑6) in the bronchoalveolar lavage fluid (BALF), and the expression levels of Bcl‑2 homologous antagonist/killer (Bak), Bcl‑2, pro‑caspase‑3, cleaved caspase‑3 and the phosphorylation of ERK1/2 in the lung tissues were measured. Propidium iodide uptake and TUNEL staining were used to detect epithelial cell death. The Dex pretreatment group exhibited fewer pathological changes, lower W/D ratios and lower expression levels of inflammatory cytokines in BALF compared with the VILI group. Dex significantly attenuated the ratio of Bak/Bcl‑2, cleaved caspase‑3 expression levels and epithelial cell death, and increased the expression of phosphorylated ERK1/2. The protective effects of Dex could be partially reversed by PD98059, which is a mitogen‑activated protein kinase (upstream of ERK1/2) inhibitor. Overall, dexmedetomidine was found to reduce the inflammatory response and epithelial cell death caused by VILI, via the activation of the ERK1/2 signaling pathway.

Although peroxisome proliferator-activated receptor (PPAR)-α has been reported to be involved in preventing acute lung injury (ALI), the molecular regulation of post‑ALI lung recovery remains to be fully elucidated. The aim of the present study was to characterize the mechanism by which PPAR‑α prevents ALI and examine the role of PPAR‑α in the recovery of lung function following acute respiratory distress syndrome (ARDS). Reverse transcription‑quantitative‑polymerase chain reaction and western blot analyses suggested that PPAR‑α was effective in suppressing transforming growth factor (TGF)‑β1 in HLF cells and RAW 264.7 cells. In an ALI mouse model, PPAR‑α treatment prior to stimulation with lipopolysaccharide (LPS) resulted in a decrease in the expression of TGF‑β1 in bronchoalveolar lavage fluid (BALF), peripheral blood and splenocytes. The injection of a virus expressing short hairpin PPAR‑α into mice following LPS treatment resulted in a dose‑dependent increase in lung resistance index and decrease in dynamic compliance, and a significant increase in BALF protein, which indicated PPAR‑α was essential for the recovery of lung function following ALI. Of note, the serum expression of PPAR‑α was inversely correlated with TGF‑β1 and negatively correlated with disease severity in patients with ARDS. These data suggested that PPAR‑α was essential for the recovery of lung function following ALI by the suppression of TGF‑β1, which reveals a previously unappreciated mechanism controlling post‑ALI lung recovery.

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.

Among a number of clinical factors, bacterial infection is one of the most common causes of acute lung injury (ALI), a serious complication that carries a high risk of mortality (~40%). During the process of ALI, intense local and systemic inflammation is elicited, which exacerbates the injury. Neutrophil infiltration into airspace is observed in early stage of ALI, and is required for the full development of ALI through an array of mechanisms, including the release of granule contents and the production of pro‑inflammatory cytokines, due to the overactivation of complement and cytokines. The present study noted that ethyl pyruvate alleviated ALI in lipopolysaccharide (LPS)‑induced ALI mice. Increased autophagy in neutrophils from ALI mice was observed, while ethyl pyruvate diminished autophagy in neutrophils and constrained granule release, and therefore myeloperoxidase (MPO) in bronchoalveolar lavage fluid and the production of proinflammatory cytokines. Using neutrophil cells, it was identified that autophagy was required for neutrophil activation and granule release, and that ethyl pyruvate caused neutrophil autophagy, leading to the restriction of granule release, and thus contributing to the mitigation of ALI. If autophagy was obviated through knockdown of key regulator of autophagy Atg5, the effects of ethyl pyruvate on granule release by neutrophils disappeared. Taken together, the results demonstrated that ethyl pyruvate alleviates ALI through inhibition of autophagy‑induced granule release by neutrophils, and this mechanism suggested a novel potential therapeutic target in autophagy regulation for ALI.