Lung Injury In Mice Research Articles

Silencing of lncRNA Gm26917 Attenuates Alveolar Macrophage-mediated Inflammatory Response in LPS-induced Acute Lung Injury Via Inhibiting NKRF Ubiquitination.

The inflammatory response mediated by alveolar macrophages plays a crucial role in the development of acute lung injury. Numerous studies have reported that lncRNAs are highly expressed in acute lung injury in mouse models and cell lines, and acute lung injury (ALI) can be effectively alleviated by targeting these lncRNAs. The aim of this study was to explore the mechanism by LncRNA Gm26917 regulates the inflammatory response in alveolar macrophages during acute lung injury mouse model. We initially observed a significant upregulation of Gm26917 expression in both ALI conditions and in MH-S cells treated with LPS. Furthermore, the silencing of Gm26917 via lentivirus-mediated methods conferred protection against LPS-induced ALI. Additionally, siRNA-mediated knockdown of Gm26917 attenuated LPS-induced inflammatory responses and modulated the function of alveolar macrophages. Subsequent mechanistic studies revealed that Gm26917 interacts with NKRF, and its knockdown suppressed NKRF ubiquitination, thereby enhancing NKRF binding to p50 and subsequently inhibiting the NF-κB signaling pathway. In conclusion, our findings demonstrate that silencing Gm26917 can mitigate LPS-induced ALI by modulating the NF-κB signaling pathway in alveolar macrophages through interactions with NKRF.

Protective effect and mechanism of Sufentanil on acute lung injury in septic mice

Protective effect and mechanism of Sufentanil on acute lung injury in septic mice

Endarachne binghamiae Extract Ameliorates Inflammatory Responses in Macrophages Through Regulation of MAPK, NF-kB and PI3K/AKT Pathways, and Prevents Acute Lung Injury in Mice

In this study, the anti-inflammatory effect of the hot water extract of Endarachne binghamiae (EB-WE), a type of marine brown algae, was investigated in LPS-stimulated RAW 264.7 cells and an acute lung injury (ALI) mouse model induced by intranasal LPS administration. Treatment with EB-WE significantly inhibited NO and pro-inflammatory cytokine (TNF-a and IL-6) production in LPS-stimulated RAW 264.7 cells. In mRNA analysis, the expression of pro-inflammatory cytokines, COX-2, and iNOS mRNAs, was down-regulated by EB-WE treatment. The phosphorylation of MAPK, IkB, and PI3K/AKT molecules responsible for signal pathways during inflammation in LPS-stimulated macrophages was also significantly inhibited by EB-WE. In an in vivo model for ALI, oral administration of EB-WE significantly reduced the level of pro-inflammatory cytokines (TNF-a, IL-1b, and IL-6) and chemokines (MCP-1, CXC-16, CXCL1, and TARC) in serum or bronchoalveolar lavage fluid (BALF) of mice. Similarly to the results in LPS-stimulated RAW 264.7 cells, treatment with EB-WE significantly inhibited intracellular signal pathways mediated by MAPK, IkB, and PI3K/AKT in lung tissues of mice with ALI, and also decreased the expression of mRNAs of inflammatory mediators such as TNF-a, IL-6, iNOS, and COX-2. Furthermore, the inhibitory effect of EB-WE on ALI was apparently confirmed in histological examination through lung tissue staining. Taken together, it is clear that EB-WE has potential activity to effectively ameliorate the inflammatory responses in macrophages through down-regulation of MAPK, NF-kB, and PI3K/AKT activation, and suppress acute lung injury induced by LPS. These findings strongly suggest that EB-WE is a promising natural product beneficial for developing preventive treatments and cures of inflammation-related diseases.

The Mechanism of Baicalin in the Treatment of Mycoplasma Pneumoniae Pneumonia by Regulating NLRP3/Caspase-1 Signaling Pathway

ABSTRACT Objective This study investigated the mechanism of baicalin (BIA) attenuating the inflammatory response and lung injury in mycoplasma pneumoniae pneumonia (MPP) mice. Methods MPP mouse models were established and then treated with BIA, azithromycin, or NLRP3 inflammasome activator. Lung wet-to-dry weight (W/D) ratio were weighed. Serum levels of MP-IgM, C-reactive protein (CRP) and bronchoalveolar lavage fluid (BALF) protein were detected by kits, NLRP3/Caspase-1 pathway-related protein levels by Western blot, and IL-1β, IL-18, IL-6 and TNF-α levels by ELISA. HE staining was performed to detect lung injury. Results MPP mice showed elevated mouse lung W/D ratio, upregulated serum MP-IgM and CRP levels and BALF protein, and enhanced IL-6 and TNF-α levels, which were reversed by BIA or azithromycin treatment, suggesting that BIA attenuated pulmonary inflammatory response in MPP mice. The lung tissue of MPP mice showed upregulated NLRP3, cleaved Caspase-1,Caspase-1, GSDMD-N and GSDMD levels and raised IL-1β and IL-18 levels, and changes were annulled by BIA or azithromycin treatment, suggesting that BIA inhibited the NLRP3/Caspase-1 pathway activation. NLRP3/Caspase-1 pathway activation partially abrogated the alleviative effect of BIA on the pulmonary inflammatory response of MPP mice. Conclusion BIA mitigates inflammatory response and lung injury in MPP mice by inhibiting NLRP3/Caspase-1 pathway activation.

Induction of age-related ocular disorders in a mouse model of pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease linked to aging. This study investigates potential connections between IPF and age-related eye problems using a bleomycin-induced IPF mouse model. Intratracheal administration of bleomycin induces rapid lung injury in mice, followed by IPF with characteristics of cellular senescence. IPF-injured mice had reduced amplitudes of scotopic ERG and immunostaining of visual arrestin, suggesting declined rod-related visual function. Interestingly, the mice's eyes also showed increased susceptibility to Staphylococcus aureus infections, reminiscent of the aging eyes. To determine whether an early onset of aging contributes to the eye disorders, we examined complement and senescence markers in the retina. In bleomycin-injury IPF mice, DNA damage-related senescence marker γH2AX was found in the retinal out nuclear layer where photoreceptors are located. Additionally, IPF mice displayed elevated levels of C3b, a complement fragment resulting from C3 activation that occurs frequently in aging eyes. These findings underscore the potential of IPF as a valuable mouse model for investigating early-onset age-related ocular disorders.

SNHG16 alleviates pulmonary ischemia-reperfusion injury by promoting the warburg effect through regulating MTCH2 expression: experimental studies.

Pulmonary ischemia-reperfusion injury (PIRI) is a major cause of fatality post-lung transplantation. Though some long non-coding RNAs (lncRNAs) have been studied in acute lung injury (ALI), their effects on PIRI remain undefined. The present study aims to explore the underlying mechanism of small nucleolar RNA host gene 16 (SNHG16) in PIRI. PIR mouse and OGD/R cell models were established. Exosomes were extracted from human pulmonary microvascular endothelial cells (HPMECs). Functional and rescue experiments were conducted in OGD/R-exposed HPMECs, OGD/R-exposed pulmonary alveolar epithelial type II cells (AECs), and I/R model mice. The relationships among SNHG16, miR-372-3p/miR-373-3p, and MTCH2 were also verified using dual luciferase reporter assay, RNA pull-down and RIP assay. SNHG16 was downregulated in OGD/R-exposed HPMECs, and SNHG16 overexpression accelerated proliferation, angiogenesis, and ameliorated mitochondrial respiration in OGD/R-exposed HPMECs. HPMEC-derived exosomal SNHG16 suppressed OGD/R-induced type II AEC injury. SNHG16 ameliorated lung injury in PIR mice. Mechanistically, SNHG16 targeted and negatively regulated miR-372-3p and miR-373-3p expression, and MTCH2, a target gene of miR-372-3p/miR-373-3p. SNHG16 was found to upregulate MTCH2 expression not only in a miR-372-3p and miR-373-3p-dependent manner but also suppress ubiquitination induced MTCH2 degradation. Our findings revealed that SNHG16 overexpression suppressed OGD/R-induced HPMEC apoptosis by promoting Warburg effect, and HPMEC-derived exosomal SNHG16 alleviated PIRI through the miR-372-3p/miR-373-3p/MTCH2 axis, suggesting that SNHG16 as a therapeutic target for PIRI.

Phosphorylated polysaccharides derived from Scrophulariae Radix mitigates lipopolysaccharide (LPS)-induced acute lung injury in mice by suppressing the NF-κB-mediated inflammatory response

ABSTRACT Acute lung injury (ALI) is a severe form of diffuse lung disease that poses a significant health burden in clinical settings. Numerous natural compounds derived from plants have shown effective anti-inflammatory activities with low toxicity, particularly polysaccharides, which have garnered considerable attention. This study explores key aspects of the pathogenesis of ALI and the potential mitigation effects of phosphorylated polysaccharides derived from Scrophulariae Radix (PPSR) in a lipopolysaccharide (LPS)-induced mouse model of ALI. These include alterations in the lung tissue wet/dry ratio, histopathological changes, modulation of pro-inflammatory cytokines, and inhibition of the NF-κB signalling pathway. Moreover, PPSR significantly reduced lung nitric oxide (NO) production and the expression of inducible NO synthase (iNOS) in lung tissue. The findings provide important insights into the mechanisms underlying the therapeutic effects of PPSR, emphasising its anti-inflammatory properties and its potential to alleviate the detrimental consequences of ALI.

Inhibition of GBP5 activates autophagy to alleviate inflammatory response in LPS-induced lung injury in mice

Background Pulmonary emphysema is a condition that causes damage to the lung tissue over time. GBP5, as part of the guanylate-binding protein family, is dysregulated in mouse pulmonary emphysema. However, the role of GBP5 in lung inflammation in ARDS remains unveiled. Methods To investigate whether GBP5 regulates lung inflammation and autophagy regulation, the study employed a mouse ARDS model and MLE-12 cell culture. Vector transfection was performed for the genetic manipulation of GBP5. Then, RT-qPCR, WB and IHC staining were conducted to assess its transcriptional and expression levels. Histological features of the lung tissue were observed through HE staining. Moreover, ELISA was conducted to evaluate the secretion of inflammatory cytokines, autophagy was assessed by immunofluorescent staining, and MPO activity was determined using a commercial kit. Results Our study revealed that GBP5 expression was altered in mouse ARDS and LPS-induced MLE-12 cell models. Moreover, the suppression of GBP5 reduced lung inflammation induced by LPS in mice. Conversely, overexpression of GBP5 diminished the inhibitory impact of LPS on ARDS during autophagy, leading to increased inflammation. In the cell line of MLE-12, GBP5 exacerbates LPS-induced inflammation by blocking autophagy. Conclusion The study suggests that GBP5 facilitates lung inflammation and autophagy regulation. Thus, GBP5 could be a potential therapeutic approach for improving ARDS treatment outcomes, but further research is required to validate these findings.

CircTLK1 Knockdown Alleviates Cell Inflammation and Apoptosis by Regulating Elavl1/Nox4 Axis in Neonatal Sepsis-Induced Lung Injury in Mice.

Septic acute lung injury (ALI) is a common complication of sepsis with high morbidity and mortality but lacks specific treatment. This study aimed to elucidate the role of circular RNA TLK1 (circTLK1) in neonatal septic ALI. Murine cecal slurry was used to induce neonatal sepsis-induced ALI model in vivo. Hematoxylin and eosin staining was performed to detect the pathological changes in lung tissues. Pulmonary microvascular endothelial cells were treated with lipopolysaccharide (LPS) to induce neonatal sepsis-induced ALI model in vitro. The levels of IL-1β and IL-6 were detected by enzyme-linked immunosorbent assay. A lactate dehydrogenase (LDH) detection kit was used to detect LDH activity. Cell Counting Kit-8 assay and flow cytometry detected cell viability and apoptosis. The genes' expression was measured by quantitative real-time reverse-transcription polymerase chain reaction and western blot. The relationship between circTLK1 and Elavl1 or Elavl1 and Nox4 was detected using RNA immunoprecipitation assay. Our results illustrated that circTLK1 was highly expressed in neonatal sepsis-induced ALI model, and circTLK1 knockdown alleviated cell inflammation and apoptosis in neonatal sepsis-induced ALI model. Similarly, we found that circTLK1 knockdown alleviated neonatal sepsis-induced ALI. Mechanically, circTLK1 mediated Elavl1 binding to Nox4 messenger RNA and increased its stability. Functionally, circTLK1 knockdown alleviated cell inflammation and apoptosis by regulating Nox4 in the neonatal sepsis-induced ALI model. CircTLK1 knockdown alleviated cell inflammation and apoptosis by the Elavl1/Nox4 axis in neonatal sepsis-induced ALI. Our research provided a novel direction for the treatment of neonatal sepsis-induced ALI. · CircTLK1 knockdown relieved neonatal septic ALI.. · CircTLK1 mediated Elavl1 binding to Nox4 mRNA..

Enhanced itaconic acid secretion from macrophages mediates the protection of mesenchymal stem cell-derived exosomes on lipopolysaccharide-induced acute lung injury mice.

Alveolar macrophages (AMs) is critical to exacerbate acute lung injury (ALI) induced by lipopolysaccharide (LPS) via inhibiting inflammation, which could by shifted by mesenchymal stem cell-derived exosomes (MSC-exos). But the underlying rationale is not fully clarified. Our study aimed to analyze the significance of itaconic acid (ITA) in mediating the protective effects of MSC-exos on LPS-induced ALI. MSC-exos were used to treat pulmonary microvascular endothelial cells (PMVECs) co-cultured with AMs under LPS stimulation. si-IRG1 was transfected to AMs. PMVEC permeability, apoptosis rates, and inflammatory cytokine levels were assessed. In vivo, C57BL/6 wild-type (WT) and Irg1-/- mice were employed to explore the protection of MSC-exos against LPS-induced ALI. The lung injury was determined by histological and biochemical assays. ITA levels were measured using gas chromatography-mass spectrometry. Western blot and flow cytometry analyses were performed to assess M1/M2 polarization. Co-culture with AMs significantly increased PMVEC permeability, apoptosis rates, IL-6, TNF-α levels and Claudin-5 and ZO-1 expression induced by LPS treatment, which were attenuated by MSC-exos accompanied by enhanced ITA level. After si-IRG1 transfection, MSC-exos' protective efficacy was reversed, with suppressed M2 polarization. In vivo, MSC-exos alleviated alveolar structure disruption, pulmonary edema, inflammation and increased ITA concentration in WT mice but had reduced effects in Irg1-/- mice, with neglected M2 polarization. ITA secretion facilitated the MSC-exos' protective benefits on LPS-induced PMVEC damage and ALI in mice by promoting AM M2 polarization, highlighting a potential therapeutic strategy for ALI and related inflammatory lung diseases.

Protective effect of Streptococcus salivarius K12 against Mycoplasma pneumoniae infection in mice

To investigate the protective effect of the probiotic bacterium Streptococcus salivarius K12 (K12) against Mycoplasma pneumoniae (Mp) infection in mice. Forty male BALB/c mice were randomized into normal control group, K12 treatment group, Mp infection group, and K12 pretreatment prior to Mp infection group. The probiotic K12 was administered daily by gavage for 14 days before Mp infection induced by intranasal instillation of Mp. Three days after Mp infection, the mice were euthanized for analysis of bronchoalveolar lavage fluid (BALF) cell counts and serum levels of secretory immunoglobulin A (sIgA), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6). RT-qPCR was performed to detect the P1 and community-acquired respiratory distress syndrome ( CARDS ) toxin of Mp in the lung tissues and the mRNA expressions of TNF-α, IL-6, chemokine 1 (CXCL1), matrix metalloproteinase 9 (MMP9), mucin 5ac (MUC5ac), collagen 3a1 (Col3a1), Toll-like receptor 2 (TLR2) and TLR4; the protein expressions of TLR2 and TLR4 in the lung tissue were detected using Western blotting. Pathological changes in the lung tissue and airway remodeling were examined with HE staining and AB/PAS staining. Compared with the Mp-infected mice with PBS treatment, the infected mice with K12 treatment showed significantly lowered mRNA levels of P1 and CARDS in the lung tissue and reduced white blood cell counts in the BALF (P<0.05). In spite of the absence of significant differences in serum levels of inflammatory factors between the two groups, the mRNA expressions of TNF‑α, IL-6, CXCL1, MMP9, MUC5ac and COL3A1 and the mRNA and protein levels of TLR2 and TLR4 in the lung tissues were significantly lower in K12-treated mice, in which AB/PAS staining showed obviously decreased mucus secretion. K12 pretreatment can effectively reduce pulmonary inflammatory responses, improve airway remodeling and alleviate lung injury in Mp-infected mice.

Isoliquiritigenin Exhibits Anti-Inflammatory Responses in Acute Lung Injury by Covalently Binding to the Myeloid Differentiation Protein-2 Domain.

Acute lung injury (ALI), a systemic inflammatory response with high morbidity, lacks effective pharmacological therapies. Myeloid differentiation protein-2 (MD2) has emerged as a promising therapeutic target for ALI. Herein, we aimed to evaluate the ability of isoliquiritigenin (ISL), a natural flavonoid found in licorice as a novel MD2 inhibitor, to inhibit lipopolysaccharide (LPS)-induced ALI. We established a mouse ALI model and a RAW 264.7 cell injury model through LPS administration. Then, lung injury was assessed through histopathological examination, and the effects of ISL were evaluated using immunofluorescence, western blotting, reverse transcription-quantitative polymerase chain reaction, flow cytometry, and enzyme-linked immunosorbent assays. In addition, the interaction between ISL and MD2 was investigated through co-immunoprecipitation and LPS displacement assays. Molecular docking and liquid chromatography/mass spectrometry analyses were employed to predict the ISL-binding domain of MD2. We found that ISL covalently bound to the Cysteine 133 residue of MD2, disrupting the formation of the LPS/MD2/toll-like receptor 4 complex, and ISL significantly suppressed proinflammatory cytokine production and reactive oxygen species generation in LPS-induced RAW264.7 cells. Moreover, ISL significantly alleviated lung injury in LPS-induced mice, reducing pulmonary microvascular permeability, inflammatory cell infiltration, and inflammatory cytokine expression. The underlying mechanism of ISL involved the inhibition of nuclear factor kappa B and the p38 mitogen-activated protein kinase pathway. Our findings supported that MD2 is the direct target of ISL in mediating its anti-inflammatory response invivo and invitro, and it holds potential as a therapeutic candidate for treating ALI and other inflammatory diseases.

Nerelimomab Alleviates Capsaicin-Induced Acute Lung Injury by Inhibiting TNF Signaling and Apoptosis.

Background: Capsaicin is commonly used as a flavoring and a riot control agent. However, long-term exposure or high doses can cause acute lung injury in military and police personnel. The mechanisms underlying capsaicin-induced pulmonary toxicity remain unclear. Therefore, this study investigated the molecular mechanisms involved in capsaicin-induced acute lung injury using C57BL/6N mice. Methods: Through both transcriptomic and proteomic analyses of mouse lung tissue, we identified the involvement of the TNF signaling pathway in capsaicin-mediated acute lung injury. Next, we explored the role of TNF signaling in the progression of acute lung injury to identify potential therapeutic targets. In a capsaicin-induced acute lung injury mouse model and A549 cells, we assessed the therapeutic potential of the TNF-α antibody Nerelimomab. Compared with the control group, TNF-α up-regulation was observed, which correlated with increased pathological changes and elevated IL-6 (p < 0.01) and IL-18 (p < 0.01) levels, both in vivo and in vitro. Results: Flow cytometry revealed that compared to the capsaicin group, Nerelimomab treatment reduced the number of capsaicin-induced apoptotic cells (p < 0.001) and was associated with an increased Bcl-2/Bax ratio (p < 0.01) and reduced cleaved caspase 3 expression (p < 0.001). Analysis of A549 cells treated with capsaicin and Nerelimomab corroborated these results. These findings confirm the involvement of the TNF signaling pathway in capsaicin-induced acute lung injury and the apoptosis of alveolar epithelial cells. Conclusions: In conclusion, capsaicin inhalation can cause acute lung injury, and targeting the TNF signaling pathway offers a promising therapeutic strategy. Nerelimomab demonstrates significant potential in alleviating acute lung injury by inhibiting inflammatory mediator release and diminishing apoptosis. Based on transcriptomic and proteomic analyses, this study highlights the crucial role of the TNF signaling pathway in capsaicin-induced acute lung injury and supports the therapeutic efficacy of Nerelimomab in reducing epithelial apoptosis.

Ozone therapy ameliorates lipopolysaccharide-induced acute lung injury in mice by inhibiting the NLRP3/ASC/caspase-1 axis.

Ozone therapy ameliorates lipopolysaccharide-induced acute lung injury in mice by inhibiting the NLRP3/ASC/caspase-1 axis.

A chimeric peptide promotes immune surveillance of senescent cells in injury, fibrosis, tumorigenesis and aging.

The accumulation of senescent cells can lead to tissue degeneration, chronic inflammatory disease and age-related tumorigenesis. Interventions such as senolytics are currently limited by off-target toxicity, which could be circumvented by instead enhancing immune-mediated senescent cell clearance; however, immune surveillance of senescent cells is often impeded by immunosuppressive factors in the inflammatory microenvironment. Here, we employ a chimeric peptide as a 'matchmaker' to bind to the urokinase-type plasminogen activator receptor, a cell surface marker of senescent cells. This peptide modifies the cell surface with polyglutamic acid, promoting immune cell-mediated responses through glutamate recognition. By enhancing the recruitment of immune cells and directly coupling senescent cells and immune cells, we show that this chimeric peptide induces immune clearance of senescent cells and restores tissue homeostasis in conditions such as liver fibrosis, lung injury, cancer and natural aging in mice. This chimeric peptide introduces an immunological conversion strategy that rebalances the senescent immune microenvironment, offering a promising direction for aging immunotherapy.

Maternal Lactobacillus johnsonii supplementation attenuates hyperoxia-induced lung injury in neonatal mice through microbiota regulation.

Supplemental oxygen impairs lung development in premature infants with respiratory distress. This study investigated the effects of maternal Lactobacillus johnsonii supplementation on hyperoxia-induced lung injury in neonatal mice. Pregnant C57BL/6 mice received L. johnsonii in normal saline (NS) from gestational days 16-21. Control pregnant mice received an equal volume of NS. After birth, the pups were exposed to hyperoxia (O2) or room air (RA) for 1 week. Four groups were studied: NS+RA, probiotic+RA, NS+O2, and probiotic+O2. On postnatal day 7, the lung and intestinal microbiota were sampled, and the right lung was analyzed. Compared to the NS+RA, probiotic+RA, and probiotic+O2 groups, the NS+O2 group exhibited significantly lower body weight, lung vascular density, and more significant mean linear intercept, IL-6, and 8-OHdG. In the genus level of gut microbiota, the NS+O2 group showed considerably more Staphylococcus and less Lactobacillus than the other three groups. The outcomes showed that in neonatal mice exposed to hyperoxia, maternal L. johnsonii supplementation improved lung development, decreased IL-6 and 8-OHdG levels, and restored gut microbiota. Maternal L. johnsonii supplementation reduced lung inflammation and improved lung development in hyperoxia-exposed neonatal mice. The mechanism may be related to the gut microbiota, as L. johnsonii improved gut microbiota communities and regulated dysregulated metabolic pathways.

Fuzheng Jiedu decoction alleviates H1N1 virus-induced acute lung injury in mice by suppressing the NLRP3 inflammasome activation.

Severe influenza, marked by excessive cytokine production, is a major contributor to death in hospitalized individuals. Fuzheng Jiedu decoction (FZJDD), an effective traditional Chinese herbal recipe, has demonstrated promising results in combating the COVID-19 pandemic by reducing mortality and improving Symptoms, and has exhibited anti-inflammatory properties in both clinical trials and laboratory research. Given that pneumonia is a common outcome of SARS-CoV-2 and H1N1 virus infections, we hypothesized that FZJDD may also have therapeutic effects on influenza-related pneumonia and acute lung injury (ALI). This research sought to explore the impact and underlying mechanisms of FZJDD on ALI caused by the H1N1 virus in mice. FZJDD was characterized using UHPLC-MS/MS. A mouse model infected with H1N1 virus was used to examine the therapeutic and protective benefits of FZJDD in a living organism, by monitoring body weight fluctuations, lung index, histopathological changes, lung injury scores, and survival rates. Lung tissues underwent haematoxylin-eosin staining, western blotting, qRT-PCR and plaque reduction assay. Blood serum was gathered to assess levels of IL-1β, IL-6, TNF-α through ELISA testing. The impact of FZJDD on the NLRP3 inflammasome was further evaluated in macrophages. FZJDD treatment significantly mitigated weight loss, reduced lung index, alleviated histopathological injury, and improved the survival rates in mice with H1N1 virus-induced ALI, demonstrating a protective effect against influenza virus infection. qRT-PCR and Western blot assays revealed that FZJDD treatment ameliorated the hyperinflammatory response caused by the H1N1 virus in lung tissue by suppressing NLRP3 inflammasome activation, without impacting viral replication. In vitro experiments additionally verified that FZJDD treatment can suppress the activation of the NLRP3 inflammasome triggered by the H1N1 virus. Our findings demonstrate that FZJDD treatment can mitigate ALI caused by H1N1 virus and enhance the survival rate in mice, while it doesn't lower viral titers in the lungs. FZJDD achieves these outcomes by curbing excessive inflammation and blocking the activation of NLRP3 inflammasome.

Hyperbaric Oxygen Protects Acute Lung Injury Secondary to Deinagkistrodon Acutus Venom Poisoning by Regulating Th17/Treg Balance.

To explore the mechanism of hyperbaric oxygen (HBO) intervention on acute lung injury secondary to Deinagkistrodon acutus snake venom poisoning and provide more toxicological and clinical evidence for Deinagkistrodon acutus venom poisoning. Male Kunming mice (n = 96) were randomly divided into four groups: the control group which was not given any interventional treatments, venom group in which each mouse was injected with Deinagkistrodon acutus venom (1 mg/kg) through the tail vein, antivenom group in which each mouse was injected with anti-Deinagkistrodon acutus venom immediately after the model was successfully established, and HBO+antivenom group in which each mouse was given HBO treatment at 1 h, 5 h, 11 h and 23 h following the injection of antivenom. Lung tissues of mice were obtained and processed for the detection of the lung coefficient, the levels of inflammatory factors such as interleukin (IL)-6, IL-10 and IL-17, and the protein expression of retinoic acid receptor (RAR)-related orphan receptor gamma (RORγt) and forkhead box P3 (FOXP3). Separate lung tissue specimens were acquired for hematoxylin-eosin staining. Compared with the venom group, HBO+antivenom group exhibited (1) improved survival rate within 24 h; (2) resolution of pulmonary edema, integrity restoration of alveolar structure, and reduced number of infiltrated inflammatory cells; (3) diminished levels of pro-inflammatory factors and increased abundance of anti-inflammatory factors beginning 2 h after envenomation; and (4) balanced expression of RORγt protein and FOXP3 protein at 24 h after envenomation. HBO combined with antivenom can significantly relieve secondary lung injury in mice poisoned with Deinagkistrodon acutus venom by immediately regulating the balance of helper T cell 17 (Th17)/regulatory T cell (Treg) related proteins.

Effects of Cd177 knockout on lung injury and colonic barrier in mice with acute pancreatitis

Effects of Cd177 knockout on lung injury and colonic barrier in mice with acute pancreatitis

Exacerbation of pulmonary fibrosis following acute lung injury via activin-A production by recruited alveolar macrophages.

Acute respiratory distress syndrome (ARDS) is a complicated pathological cascade process of excessive pulmonary inflammation and alveolar epithelial cell apoptosis that results in respiratory dysfunction and failure. Some cases of ARDS can result in a more severe state of pulmonary fibrosis, referred to as postinjury lung fibrosis. The mortality and incidence rate of ARDS are high, particularly when it leads to continuing alveolar and interstitial fibrosis, which requires urgent treatment and appropriate management. The lipopolysaccharide (LPS)-induced acute lung injury (ALI) mouse model has been widely implemented for studying ARDS in humans. In our study, we found alterations in the alveolar macrophage (AM) profile in such a mouse model. Specifically, activin-A produced by dominantly recruited AMs (recAMs) was noted to be implicated in the process of post-injury lung fibrosis. The ALI animal model in C57BL/6 mice was established via 3.5 mg/kg of LPS intratracheal administration. Single-cell RNA (scRNA) sequencing was used for detailed classification and functional characterization of lung macrophages. Through in vivo experiments, we evaluated the role that activin-A plays in post-injury lung fibrosis in an ALI mouse model using enzyme-linked immunosorbent assay (ELISA), histological staining methods, and immunofluorescence. Through in vitro experiments, we analyzed the effect of activin-A on murine lung epithelial 12 (MLE-12) cells and bone marrow-derived macrophages (BMDMs) using Western blotting (WB), quantitative real-time polymerase chain reaction, RNA sequencing, and immunofluorescence. Our findings revealed that recAMs replaced tissue-resident alveolar macrophages (TRAMs) as the dominant macrophage population in the setting of ALI. The results of Gene Ontology (GO) analysis suggested that activin-A was associated with wound healing and suppressor of mothers against decapentaplegic (SMAD) protein signaling pathways. Immunofluorescence results revealed that the receptor of activin-A mainly localized to alveolar epithelial cells and macrophages. Subsequently, activin-A was specifically found to drive MLE-12 cells to mesenchymal cell transformation via the transforming growth factor-β (TGF-β)/SMAD signaling. Moreover, the results of transcriptome analysis and WB confirmed that activin-A could enhance the concerted activity of Hippo and TGF-β/SMAD pathways in BMDMs, leading to an increased expression of profibrotic mediator. Moreover, yes-associated protein (YAP) and transcriptional coactivated with PDZ-binding motif (TAZ) proteins were found to drive BMDM activin-A expression, which could generate a positive feedback mechanism that perpetuates fibrosis. Our findings revealed that activin-A is involved in the pathological mechanisms in post-injury lung fibrosis by promoting epithelial-mesenchymal transition (EMT) and the formation of an underlying profibrotic positive feedback loop in recAMs. Activin-A is thus a potential therapeutic target for developing ALI and ALI-associated pulmonary fibrosis therapeutics.