Inflammatory Factors In Bronchoalveolar Lavage Fluid Research Articles

Effect and mechanism of amphiregulin on acute respiratory distress syndrome in mice

To explore the protective effect of amphiregulin (Areg) on acute respiratory distress syndrome (ARDS) in mice and its underlying mechanism. (1) Male C57BL/6 mice aged 6-8 weeks were selected for animal experiments and divided into 3 groups (n = 10) according to the random number table method, which includes sham-operated group (Sham group), ARDS model group [ARDS model in mice was established by intratracheal instillation of lipopolysaccharide (LPS) 3 mg/kg] and ARDS+Areg intervention group [recombinant mice Areg (rmAreg) 5 μg was injected intraperitoneally 1 hour after LPS modeling]. The mice were sacrificed at 24 h after LPS injection lung histopathological changes were observed under hematoxylin-eosin (HE) staining and scored for lung injury; oxygenation index and wet/dry ratio of lung tissue were measured; the content of protein in bronchoalveolar lavage fluid (BALF) was detected by bicinchoninic acid (BCA) method, the level of inflammatory factors interleukins (IL-1β, IL-6) and tumor necrosis factor-α (TNF-α) in BALF were measured by enzyme-linked immunosorbent assay (ELISA). (2) Mice alveolar epithelial cell line MLE12 cells were obtained and cultured for experiment in vitro. Blank control group (Control group), LPS group (LPS 1 mg/L) and LPS+Areg group (rmAreg 50 μg/L was added 1 hour after LPS stimulation) were set. The cells and culture fluid were collected at 24 hours after LPS stimulation, and the apoptosis level of MLE12 cells was detected by flow cytometry; the activation level of phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) and the expressions of apoptosis-related proteins Bcl-2 and Bax in MLE12 cells were detected by Western blotting. (1) Animal experiments: compared with the Sham group, the lung tissue structure of ARDS model group was destroyed, the lung injury score was significantly increased, the oxygenation index was significantly decreased, the wet/dry weight ratio of lung was significantly increased, and the levels of protein and inflammatory factors in BALF were significantly increased. Compared with ARDS model group, lung tissue structure damage was reduced, pulmonary interstitial congestion, edema and inflammatory cell infiltration were significantly reduced, and lung injury score was significantly decreased (scores: 0.467±0.031 vs. 0.690±0.034) in ARDS+Areg intervention group. In addition, oxygenation index in ARDS+Areg intervention group was significantly increased [mmHg (1 mmHg ≈ 0.133 kPa): 380.00±22.36 vs. 154.00±20.74]. Lung wet/dry weight ratio (5.40±0.26 vs. 6.63±0.25), protein and inflammatory factors levels in BALF [protein (g/L): 0.42±0.04 vs. 0.86±0.05, IL-1β (ng/L): 30.00±2.00 vs. 40.00±3.65, IL-6 (ng/L): 190.00±20.30 vs. 581.30±45.76, TNF-α (ng/L): 30.00±3.65 vs. 77.00±4.16], and the differences were statistically significant (all P < 0.01). (2) Cell experiments: compared with the Control group, the number of apoptotic MLE12 cells was significantly increased in the LPS group, and the levels of PI3K phosphorylation, anti-apoptotic gene Bcl-2 level and pro-apoptotic gene Bax level were increased in MLE12 cells. Compared with the LPS group, the number of apoptosis in MLE12 cells was significantly reduced in the LPS+Areg group after administration of rmAreg treatment [(17.51±2.12)% vs. (36.35±2.84)%], and the levels of PI3K/AKT phosphorylation and Bcl-2 expression in MLE12 cells were significantly increased (p-PI3K/PI3K: 2.400±0.200 vs. 0.550±0.066, p-AKT/AKT: 1.647±0.103 vs. 0.573±0.101, Bcl-2/GAPDH: 0.773±0.061 vs. 0.343±0.071), and Bax expression was significantly suppressed (Bax/GAPDH: 0.810±0.095 vs. 2.400±0.200). The differences were statistically significant (all P < 0.01). Areg could alleviate ARDS in mice by inhibiting the apoptosis of alveolar epithelial cells through activating PI3K/AKT pathway.

Effects of total ginsenosides from Panax ginseng stems and leaves on gut microbiota and short-chain fatty acids metabolism in acute lung injury mice

This study aimed to investigate the biological effects and underlying mechanisms of the total ginsenosides from Panax ginseng stems and leaves on lipopolysaccharide(LPS)-induced acute lung injury(ALI) in mice. Sixty male C57BL/6J mice were randomly divided into a control group, a model group, the total ginsenosides from P. ginseng stems and leaves normal administration group(61.65 mg·kg~(-1)), and low-, medium-, and high-dose total ginsenosides from P. ginseng stems and leaves groups(15.412 5, 30.825, and 61.65 mg·kg~(-1)). Mice were administered for seven continuous days before modeling. Twenty-four hours after modeling, mice were sacrificed to obtain lung tissues and calculate lung wet/dry ratio. The number of inflammatory cells in bronchoalveolar lavage fluid(BALF) was detected. The levels of interleukin-1β(IL-1β), interleukin-6(IL-6), and tumor necrosis factor-α(TNF-α) in BALF were detected. The mRNA expression levels of IL-1β, IL-6, and TNF-α, and the levels of myeloperoxidase(MPO), glutathione peroxidase(GSH-Px), superoxide dismutase(SOD), and malondialdehyde(MDA) in lung tissues were determined. Hematoxylin-eosin(HE) staining was used to observe the pathological changes in lung tissues. The gut microbiota was detected by 16S rRNA sequencing, and gas chromatography-mass spectrometry(GC-MS) was applied to detect the content of short-chain fatty acids(SCFAs) in se-rum. The results showed that the total ginsenosides from P. ginseng stems and leaves could reduce lung index, lung wet/dry ratio, and lung damage in LPS-induced ALI mice, decrease the number of inflammatory cells and levels of inflammatory factors in BALF, inhibit the mRNA expression levels of inflammatory factors and levels of MPO and MDA in lung tissues, and potentiate the activity of GSH-Px and SOD in lung tissues. Furthermore, they could also reverse the gut microbiota disorder, restore the diversity of gut microbiota, increase the relative abundance of Lachnospiraceae and Muribaculaceae, decrease the relative abundance of Prevotellaceae, and enhance the content of SCFAs(acetic acid, propionic acid, and butyric acid) in serum. This study suggested that the total ginsenosides from P. ginseng stems and leaves could improve lung edema, inflammatory response, and oxidative stress in ALI mice by regulating gut microbiota and SCFAs metabolism.

Effects of different doses of methylprednisolone therapy on acute respiratory distress syndrome: results from animal and clinical studies

BackgroundThe optimal dose of glucocorticoids for acute respiratory distress syndrome (ARDS) is uncertain. This study aimed to evaluate the effects of different doses of methylprednisolone on sepsis-induced acute lung injury (ALI) rats and a cohort of moderate and severe ARDS patients.MethodsALI rats, challenged with lipopolysaccharide, were randomly received intraperitoneal injection of normal saline (model group) and different doses of methylprednisolone (0.5, 2, 8 mg/kg, named as low-, moderate- and high-dose group, respectively) for 5 days. The body weight changes of rats, inflammatory factors in bronchoalveolar lavage fluid (BALF), lung wet/dry ratio, histopathological score, and the mRNA expressions of glucocorticoid receptor α (GRα), GRβ and nuclear factor-κB (NF-κB) were measured. Forty moderate and severe ARDS patients were treated with standard of care or plus different doses of methylprednisolone (40, 80, 120 mg/day, named as low-, moderate- and high-dose group, respectively) for 5 days. Clinical outcomes were PaO2/FiO2 ratio and C-reactive protein (CRP) level at day 5, intubation rate, hospital stay, 28-day mortality, and adverse events rate.ResultsIn animal experiment, different doses of methylprednisolone could increase the body weight of rats, and reduce inflammatory factors in BALF and the degree of lung injury compared with model group. The efficacy of methylprednisolone at moderate-dose was better than that at low-dose, but was equivalent to that at high-dose, which was consistent with the differential changes in the mRNA expression of GRα, GRβ and NF-κB. In clinical study, the moderate-dose group was associated with higher PaO2/FiO2 ratio and lower CRP level. No significant difference in other clinical outcomes among groups was detected.ConclusionsThis study showed that the efficacy of methylprednisolone in ARDS treatment was not always dose-dependent due to the differential regulation of related receptors. The moderate-dose of methylprednisolone may be the potential optimal dose for ARDS treatment, which needs to be further verified by larger clinical trials.

IL-9 blockade attenuates inflammation in a murine model of mechanical ventilation-induced lung injury by inhibiting the NLRP3 inflammasome pathway.

Ventilation-induced lung injury (VILI) causes a huge economic and social burden, and its prevention and treatment have gained increasing attention in recent years. IL-9 is an important inflammatory factor, but its potential role in VILI remains unclear. This study intended to explore whether blocking IL-9 could alleviate VILI and explore its underlying mechanism. Lung injury was induced by mechanical ventilation (MV) in C57BL/6 mice. Changes in inflammatory factors and NLRP3-related proteins were assessed using quantitative reverse transcription-polymerase chain reaction, western blotting, and enzyme-linked immunosorbent assay. Subsequently, Nlrp3-/- mice were used to further elucidate the underlying mechanism. The percentage of Th9 cells in the peripheral blood, bronchoalveolar lavage fluid (BALF), and lung tissues of MV mice was increased compared to those of control mice. Treatment with anti-IL-9 mAb significantly alleviated the changes in lung histopathology, wet/dry lung proportion, total protein content, and neutrophil content in BALF induced by VILI. Additionally, administering anti-IL-9 mAb significantly downregulated the expression levels of inflammatory factors in BALF and lung tissues of mice with VILI. In addition, administering anti-IL-9 mAb inhibited NLRP3 inflammasome activation, as evidenced by the observed downregulation of NLRP3, ASC, cleaved caspase-1, and GSDMD-N. Additionally, NLRP3-deficient mice had lower lung injury induced by VILI than wild-type mice. Furthermore, the anti-IL-9 mAb only partially inhibited VILI in Nlrp3-/- mice. In MV mice, the anti-IL-9 mAb alleviated lung injury and reduced the secretion and expression of inflammatory factors partly by inhibiting the NLRP3 inflammasome pathway.

Active components of Descurainia sophia improve lung permeability in rats with allergic asthma by regulating airway inflammation and epithelial damage

The present study investigated the effect of active components of Descurainia sophia on allergic asthma and explored the underlying mechanism. SD male rats were randomly divided into a normal group(NC), a model group(M), a D. sophia decoction group(DS), a D. sophia fatty oil group(FO), a D. sophia flavonoid glycoside group(FG), a D. sophia oligosaccharide group(Oli), and a positive drug dexamethasone group(Y). The allergic asthma model was induced in rats by intraperitoneal injection of ovalbumin(OVA) and aluminum hydroxide gel adjuvant(sensitization) and atomization of OVA solution(excitation). After modeling, asthma-related indicators, tracheal phenol red excretion, inflammatory cell levels in the peripheral blood, lung permeability index(LPI), and oxygenation index(OI) of rats were detected. The pathological changes of lung tissues were observed by HE staining. Enzyme-linked immunosorbent assay(ELISA) was used to detect the content of inflammatory factors immunoglobulin E(IgE), interleukin-4(IL-4), and interferon-γ(IFN-γ) in the bronchoalveolar lavage fluid(BALF) and the content of endothelin-1(ET-1) and angiotensin-converting enzyme(ACE) in lung tissue homogenate. The serum content of nitric oxide(NO) was detected by colorimetry. Western blot was employed to determine the protein expression of Toll-like receptor 4(TLR4), nuclear factor κB-p65(NF-κB-p65), phosphorylated NF-κB-p65(p-NF-κB-p65), myosin light chain kinase(MLCK), vascular endothelial cadherin(VE cadherin), connexin 43, and claudin 5, and the mechanism of active components of D. sophia on allergic asthma was explored. As revealed by the results, the M group showed extensive infiltration of inflammatory cells around the bronchus of the lung tissues of the allergic asthma rats, thickened bronchial wall, severely deformed alveolar structure, increased number of wheezes, the content of IgE, IL-4, ET-1, and ACE, inflammatory cells, and LPI, and reduced latency of asthma, tracheal phenol red excretion, IFN-γ, NO content, and OI. After the intervention of the active components of D. sophia, the DS, FO, FG, Oli, and Y groups showed improved asthma-related indicators, tracheal phenol red excretion, and lung tissue lesions in allergic asthma rats, and the effects in the FO and Oli groups were superior. The content of inflammatory factors in BALF was recovered in the DS, FO, and Y groups and the FG and Oli groups. The number of inflammatory cells in rats was reduced in the DS and FO groups, and the FG, Oli, and Y groups to varying degrees, and the effect in the FO group was superior. DS, FO, Oli, and Y reduced ET-1, ACE, and LPI and increased NO and OI. FG recovered NO, ET-1, ACE, LPI, and OI to improve lung epithelial damage and permeability. Further investigation of inflammation-related TLR4/NF-κB pathways, MLCK, and related skeleton protein levels showed that TLR4, NF-κB-p65, p-NF-κB-p65, and MLCK levels were increased, and VE cadherin, connexin 43, and claudin 5 were reduced in the M group. DS, FO, FG, Oli, and Y could reduce the protein expression related to the TLR4 pathway to varying degrees, and regulate the protein expression of MLCK, VE cadherin, connexin 43, and claudin 5. It is inferred that the active components of D. sophia improve lung permeability in rats with allergic asthma presumedly by regulating the TLR4/NF-κB signaling pathway to improve airway inflammation, mediating MLCK and connexin, and regulating epithelial damage.

Norisoboldine Attenuates Sepsis-Induced Acute Lung Injury by Modulating Macrophage Polarization via PKM2/HIF-1α/PGC-1α Pathway.

This study aimed to investigate the effect of norisopoldine (NOR) on acute lung injury in septic mice. Lipopolysaccharide (LPS) was used to establish sepsis induced acute lung injury (ALI) in mice. The dry and wet weight of mice lung was detected, and the pathological changes of lung were observed by hematoxylin and eosin (H&E) staining. Bronchoalveolar lavage fluid (BALF) was detected. Inflammatory factors in BALF were detected by enzyme-linked immunosorbent assay (ELISA). The polarization of macrophages in lung tissue was detected by flow cytometry. The markers of M1 and M2 macrophages were detected by RT-PCR. LPS induced RAW264.7 cells were treated with NOR. Inflammatory response, macrophage polarization, glycolysis, and M2 pyruvate kinase (PKM2)/hypoxia inducible factor-1α (HIF-1α)/peroxisome proliferator activated receptor-γ co-activator 1-α (PGC-1α) signaling pathway were detected. NOR could effectively alleviate sepsis induced ALI, and reduce the number of total cells, total protein concentration, neutrophils, macrophages in BALF. NOR decreased the level of inflammatory factors and promoted macrophages from M1 to M2 type in vivo and vitro. Moreover, NOR could activated PKM2, and inhibited PKM2 from cytoplasm to nuclear, attenuated HIF-1α expression, and increased PGC-1α and peroxisome proliferator-activated receptor (PPAR)-γ expression. In addition, NOR inhibited glycolysis and promoted oxidative phosphorylation in RAW264.7 cells. Furthermore, PKM2 inhibitors could reverse the effect of NOR on PKM2/HIF-1α/PGC-1α signaling pathway in RAW264.7 cells. NOR alleviated sepsis induced AIL in mice, inhibited the inflammatory response, promote M2 polarization of macrophages through regulating PKM2/HIF-1α/PGC-1α signaling pathway.

Chicken bone marrow mesenchymal stem cells improve lung and distal organ injury

Mesenchymal stem cells (MSCs) are associated with pulmonary protection and longevity. We separated chicken bone marrow-derived mesenchymal stem cells (BM-MSCs); investigated whether BM-MSCs can improve lipopolysaccharide (LPS)-induced lung and distal organ injury; and explored the underlying mechanisms. Ninety-six male ICR (6 weeks old) mice were randomly divided into three groups: Sham, LPS, and LPS + MSC groups. The mice were intratracheally injected with 5 mg/kg LPS to induce acute lung injury (ALI). The histopathological severity of injury to the lung, liver, kidney, heart, and aortic tissues was detected. Wet/dry ratio, protein concentrations in bronchoalveolar lavage fluid (BALF), BALF cell counts, inflammatory cytokine levels in serum, inflammatory cytokine gene expression, and oxidative stress-related indicators were detected. In addition, a survival analysis was performed in sixty male ICR mice (6 weeks old, 18–20 g). This study used chicken BM-MSCs, which are easier to obtain and more convenient than other animal or human MSCs, and have MSC-associated properties, such as a colony forming ability, multilineage differentiation potential, and certain phenotypes. BM-MSCs administration significantly improved the survival rate, systemic inflammation, and the histopathological severity of lung, liver, kidney, and aortic injury during ALI. BM-MSCs administration reduced the levels of inflammatory factors in BALF, the infiltration of neutrophils, and oxidative stress injury in lung tissue. In addition, BM-MSCs administration reduced TRL4 and Mdy88 mRNA expression during ALI. Chicken BM-MSCs serve as a potential alternative resource for stem cell therapy and exert a prominent effect on LPS-induced ALI and extrapulmonary injury, in part through TRL4/Mdy88 signaling and inhibition of neutrophil inflammation and oxidative stress injury.

Effect of bronchoalveolar lavage on the clinical efficacy, inflammatory factors, and immune function in the treatment of refractory pneumonia in children.

BackgroundRefractory pneumonia is a special type of pneumonia in children. This study aimed to analyze the effect of bronchoalveolar lavage (BAL) on the clinical efficacy, inflammatory factors, and immune function in the treatment of pediatric refractory pneumonia.MethodsA total of 196 children with refractory pneumonia admitted to our hospital from January 2017 to January 2020 were enrolled and allocated to a study group (n=99) and a control group (n=97). The study group was treated with BAL treatment plus conventional treatment, and the control group was treated with conventional treatment. The clinical efficacy, time of fever regression, time of cough relief, and length of hospital stay were compared between groups. Changes in inflammatory factors, immune function, pulmonary ventilation function, and complications were analyzed. The levels of inflammatory factors in BAL fluid were compared.ResultsThe times of fever remission, cough relief, and hospital stay of the study group was shorter than those of the control group, and the total clinical effective rate of the study group was higher. At any time after treatment, the levels of interleukin-6 (IL-6), C-reactive protein (CRP), and tumor necrosis factor-alpha (TNF-α) in the study group were lower than the control group. After 3-day of treatment, IL-6, CRP and TNF-α in BAL fluid in the study group were significantly decreased compared with before treatment. Immunoglobulin A (IgA) and immunoglobulin G (IgG) levels in the study group were higher than those in the control group at any time after treatment, and immunoglobulin M (IgM) levels were lower than in the control group. The levels of oxygenation index (OI), lung dynamic compliance (Cdyn), and work of breathing (WOB) in the study group were higher than those in the control group at any time after treatment.ConclusionsBAL treatment can effectively relieve the inflammatory response, improve immune function and lung ventilation function in children with refractory pneumonia. The clinical effect is remarkable and worthy of promotion.

Ozone exposure promotes pyroptosis in rat lungs via the TLR2/4-NF-κB-NLRP3 signaling pathway

ObjectiveOzone has become a major air pollutant in recent years, which leading to a variety of lung diseases. This study aimed to explore the mechanisms of pyroptosis and related signaling pathways in ozone-induced lung injury. MethodsWe exposed 120 Wistar rats to ozone, 20 in each group (half male and half female). Ozone exposure concentrations were 0, 0.12, 0.5, 1.0, 2.0 and 4.0 ppm for 6 h. At the same time, we isolated and cultured type I alveolar epithelial cells, then intervened with high mobility group box 1 protein (HMGB1), hyaluronic acid (HA) and Toll-like receptors 2/4 (TLR2/4) inhibitor. In animal experiments, histopathological experiments, TUNEL, ELISA and biochemical indicators were performed. RT-qPCR and western blot experiments assay were used to detect the expression changes of key factors in relevant signal pathways in vivo and in vitro. ResultsAfter acute ozone exposure, the levels of lung cell injury indicators in bronchoalveolar lavage fluid (BALF), as well as the levels of inflammatory factors in BALF, blood, and lung tissue were significantly increased. Male rats were more sensitive to ozone exposure. Low-concentration ozone exposure caused mild interstitial inflammation in rat lung tissue. Severe inflammation and pulmonary edema appeared with increases in concentration. ELISA results in BALF showed that HMGB1 and HA expressions increased gradually with the increase of ozone exposure concentration. RT-qPCR and Western blot showed that when ozone concentrations increased above 0.5 ppm, the expression of nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing 3 (NLRP3), cleaved caspase-1, and N-gasdermin D (N-GSDMD) in the lung tissue increased significantly, suggesting that ozone exposure induces pyroptosis. At the same time, it was found that ozone exposure activated the nuclear factor kappa B (NF-κB) signal pathway, and increased the mRNA expressions of Toll-like receptors TLR2/4. The results of cell experiments showed that after the addition of HMGB1 and HA, the expression of NF-κB and pyroptosis related indexes increased in type I alveolar epithelial cells, while the corresponding expression decreased after the addition of TLR2/4 inhibitors. ConclusionOzone exposure causes lung injury in a dose- and gender-dependent manner, and is more severe in males. When injured, the levels of HMGB1 and HA in BALF increased, which interact with TLR 2/4 to activate the downstream NF-κB signaling pathway. Further activating the NLRP3 inflammasome complex and regulating the ozone-induced pyroptosis.

Angiotensin-converting enzyme 2 attenuates inflammatory response and oxidative stress in hyperoxic lung injury by regulating NF-κB and Nrf2 pathways.

To investigate the role of angiotensin-converting enzyme 2 (ACE2) in hyperoxic lung injury. Adult mice were exposed to 95% O2 for 72 h to induce hyperoxic lung injury, and simultaneously treated with ACE2 agonist diminazene aceturate (DIZE) or inhibitor MLN-4760. ACE2 expression/activity in lung tissue and angiotensin (Ang)-(1-7)/Ang II in bronchoalveolar lavage fluid (BALF), and the severity of hyperoxic lung injury were evaluated. The levels of inflammatory factors in BALF and lung tissue and the expression levels of phospho-p65, p65 and IkBα were measured. Oxidative parameter and antioxidant enzyme levels in lung tissue were measured to assess oxidative stress. Finally, the expression levels of nuclear factor-erythroid-2-related factor (Nrf2), NAD(P)H quinine oxidoreductase 1 (NQO1) and heme oxygenase-1 (HO-1) were measured using Western blotting. Hyperoxia treatment significantly decreased lung ACE2 expression/activity and increased the Ang II/Ang-(1-7) ratio, while co-treatment with hyperoxia and DIZE significantly increased lung ACE2 expression/activity and decreased the Ang II/Ang-(1-7) ratio. By contrast, co-treatment with hyperoxia and MLN-4760 significantly decreased lung ACE2 expression/activity and increased the Ang II/Ang-(1-7) ratio. Hyperoxia treatment induced significant lung injury, inflammatory response and oxidative stress, which were attenuated by DIZE but aggravated by MLN-4760. The NF-κB pathways were activated by hyperoxia and MLN-4760 but inhibited by DIZE. The Nrf2 pathway and its downstream proteins NQO1 and HO-1 were activated by DIZE but inhibited by MLN-4760. Activation of ACE2 can reduce the severity of hyperoxic lung injury by inhibiting inflammatory response and oxidative stress. ACE2 can inhibit the NF-κB pathway and activate the Nrf2/HO-1/NQO1 pathway, which may be involved in the underlying mechanism.

IL-17A contributes to HSV1 infection-induced acute lung injury in a mouse model of pulmonary fibrosis.

BackgroundPatients with idiopathic pulmonary fibrosis (IPF) often experience acute exacerbation (AE) after an episode of common cold.AimsTo establish a mouse model of virus infection‐induced AE‐IPF and investigate the mechanism underlying the AE‐IPF.MethodsHerpes simplex virus 1 (HSV1) was inoculated intranasally to wild‐type (WT) and IL‐17A gene knockout (IL‐17A‐/‐) mice 21 days after intratracheal administration of bleomycin (BLM).Results HSV1 infection caused acute exacerbation in mice with BLM‐induced fibrosis. Compared with the BLM+Saline mice, the mice with BLM+HSV1 showed significantly higher acute lung injury (ALI) score (P < 0.0001), lower survival rate (100% vs 21.4%, P < 0.0001), poorer lung function and higher inflammatory response representing by increased total inflammatory cells in bronchoalveolar lavage fluid (BALF) (P = 0.0323), increased proportion of Th17 cells in peripheral blood (P = 0.0004) and higher inflammatory factors in BALF. In addition, HSV1 infection increased the expression of endoplasmic reticulum stress (ERS)‐related proteins in mice with BLM‐induced fibrosis. The inhibition of ERS by tauroursodeoxycholic acid (TUDCA, an ERS inhibitor) significantly reduced the IL‐17A levels in BALF (P = 0.0140) and TH17 cells in the peripheral blood (P = 0.0084) of mice with BLM+HSV1, suggesting that suppression of ERS may reduce TH17 response in mice with AE‐IPF. Compared with WT mice with BLM+HSV1, IL‐17A‐/‐ mice with BLM+HSV1 had lower ALI score (P = 0.0119), higher survival rate (78.6% vs 21.4%, P = 0.004), improved lung function, and milder inflammatory response.Conclusions HSV1 infection in addition to BLM‐induced IPF can successfully establish AE‐IPF in mice. IL‐17A and ERS promote lung inflammation in AE‐IPF development.

Curcumin reduces lung inflammation via Wnt/β-catenin signaling in mouse model of asthma

ABSTRACTObjectives: Asthma is a chronic inflammatory, heterogeneous airway disease affecting millions of people around the world. Curcumin has been found to have anti-inflammatory and antifibrosis effects. Researchers reported that curcumin regulated Wnt/β-catenin signaling in lots of cells. However, whether curcumin regulates the levels of Wnt/β-Catenin signaling in lung tissues and DCs (dendritic cells) remains unclear. In this study, we assessed the effects of curcumin on DCs and asthma. Methods: C57BL/6 mice immunized with OVA (ovalbumin) were challenged thrice with an aerosol of OVA every second day for 8 days. Dexamethasone or curcumin was administered intraperitoneally to OVA-immunized C57BL/6 mice on day 24 once a day for 9 days. Mice were analyzed for effects of curcumin on asthma, inflammatory cell infiltration and cytokine levels in lung tissue. DCs were isolated from mouse bone morrow. The surface markers CD40, CD86 and CD11c of DCs was detected by FACS (fluorescence activated cell sorting) and the function of DCs was detected by mixed lymphocyte reaction. The expression of GSK-3β and β-catenin was detected by Western Blot. Results: Results showed that OVA increased the number of inflammatory factors in BALF (bronchoalveolar lavage fluid), elevated lung inflammation scores in mice. Curcumin dose-dependently reversed the alterations induced by OVA in the asthmatic mice. Curcumin activated Wnt/β-catenin signaling pathway in DCs and asthmatic mouse lungs. Conclusions: Curcumin could influence the morphology and function of DCs, ease asthma symptom and inflammatory reaction through the activation of Wnt/β-catenin signaling. These results provide new evidence new evidence for application of curcumin on asthma.