scholarly journals A new Bi(III)-based coordination complex: Treatment and nursing application values on pediatric pneumonia

2021 ◽  
Vol 46 ◽  
pp. 146867832110458
Author(s):  
Jianli Lu ◽  
Hong Han ◽  
Bo Li ◽  
Yanjun Han
Keyword(s):  
Lavage Fluid ◽  
Alveolar Epithelial Cells ◽  
Enzyme Linked Immunosorbent Assay ◽  
Supramolecular Network ◽  
Ampk Signaling ◽  
Alveolar Epithelial ◽  
Carboxylate Groups ◽  
Pediatric Pneumonia ◽  
Pathway Activation ◽  
Amp Activated Protein Kinase

In the current work, through applying the mixed-ligand generation method, [Bi4Cl8(PDC)2 (2,2′-bpy)4]·2MeCN (1), a fresh bismuth (III)-organic compound synthesized with the solvothermal reactions between 2,2′-bipyridine (2,2′-bpy); 2,6-pyridinedicarboxylic acid (H2PDC); and bismuth chloride. The structural characterization results show that complex 1 features a binuclear discrete structure which is further extended into a 1D chain–like supramolecular network via π–π interactions. Furthermore, the compound’s treatment and nursing application values on pediatric pneumonia was explored and the novel compound’s corresponding mechanism was also investigated. First of all, in our research, the enzyme-linked immunosorbent assay (ELISA) detection kit was employed for the determination of the inflammatory cytokines content released into alveolar lavage fluid. Subsequently, the adenosine 5‘-monophosphate (AMP)–activated protein kinase (AMPK) signaling pathway activation in alveolar epithelial cells was explored exploiting the real-time reverse transcription–polymerase chain reaction (RT-PCR). Molecular docking demonstrated that although multiple pyridine rings are presented in the Bi complex, however, only the carboxylate groups have been observed to interact with the active residues.

scholarly journals Flagellin/TLR5 Stimulate Myeloid Progenitors to Enter Lung Tissue and to Locally Differentiate Into Macrophages

2021 ◽  
Vol 12 ◽  
Author(s):  
Xin Lei ◽  
Jara Palomero ◽  
Iris de Rink ◽  
Tom de Wit ◽  
Martijn van Baalen ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Low Frequency ◽  
Lavage Fluid ◽  
Lung Lavage ◽  
Alveolar Epithelial Cells ◽  
Mouse Bone Marrow ◽  
Alveolar Epithelial ◽  
Toll Like Receptor 5

Toll-like receptor 5 (TLR5) is the receptor of bacterial Flagellin. Reportedly, TLR5 engagement helps to combat infections, especially at mucosal sites, by evoking responses from epithelial cells and immune cells. Here we report that TLR5 is expressed on a previously defined bipotent progenitor of macrophages (MΦs) and osteoclasts (OCs) that resides in the mouse bone marrow (BM) and circulates at low frequency in the blood. In vitro, Flagellin promoted the generation of MΦs, but not OCs from this progenitor. In vivo, MΦ/OC progenitors were recruited from the blood into the lung upon intranasal inoculation of Flagellin, where they rapidly differentiated into MΦs. Recruitment of the MΦ/OC progenitors into the lung was likely promoted by the CCL2/CCR2 axis, since the progenitors expressed CCR2 and type 2 alveolar epithelial cells (AECs) produced CCL2 upon stimulation by Flagellin. Moreover, CCR2 blockade reduced migration of the MΦ/OC progenitors toward lung lavage fluid (LLF) from Flagellin-inoculated mice. Our study points to a novel role of the Flagellin/TLR5 axis in recruiting circulating MΦ/OC progenitors into infected tissue and stimulating these progenitors to locally differentiate into MΦs. The progenitor pathway to produce MΦs may act, next to monocyte recruitment, to fortify host protection against bacterial infection at mucosal sites.

scholarly journals Mucus production stimulated by IFN-AhR signaling triggers hypoxia of COVID-19

Cell Research ◽  
2020 ◽  
Vol 30 (12) ◽  
pp. 1078-1087 ◽  
Author(s):  
Yuying Liu ◽  
Jiadi Lv ◽  
Jiangning Liu ◽  
Man Li ◽  
Jing Xie ◽  
...  
Keyword(s):  
Intervention Strategy ◽  
Lavage Fluid ◽  
Alveolar Epithelial Cells ◽  
Mucus Production ◽  
Gas Barrier ◽  
Alveolar Epithelial ◽  
Lung Capacity ◽  
Aryl Hydrocarbon ◽  
Membrane Bound ◽  
Ifn Γ

AbstractSilent hypoxia has emerged as a unique feature of coronavirus disease 2019 (COVID-19). In this study, we show that mucins are accumulated in the bronchoalveolar lavage fluid (BALF) of COVID-19 patients and are upregulated in the lungs of severe respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected mice and macaques. We find that induction of either interferon (IFN)-β or IFN-γ upon SARS-CoV-2 infection results in activation of aryl hydrocarbon receptor (AhR) signaling through an IDO-Kyn-dependent pathway, leading to transcriptional upregulation of the expression of mucins, both the secreted and membrane-bound, in alveolar epithelial cells. Consequently, accumulated alveolar mucus affects the blood-gas barrier, thus inducing hypoxia and diminishing lung capacity, which can be reversed by blocking AhR activity. These findings potentially explain the silent hypoxia formation in COVID-19 patients, and suggest a possible intervention strategy by targeting the AhR pathway.

scholarly journals The MUC5B Mucin Is Involved in Paraquat-Induced Lung Inflammation

2020 ◽  
Vol 2020 ◽  
pp. 1-15 ◽  
Author(s):  
Hao Sun ◽  
Yunfei Jiang ◽  
Yang Song ◽  
Xiaomin Zhang ◽  
Jun Wang ◽  
...  
Keyword(s):  
Lung Inflammation ◽  
Culture Medium ◽  
Mapk Pathway ◽  
A549 Cells ◽  
Alveolar Epithelial Cells ◽  
Inflammatory Factors ◽  
Enzyme Linked Immunosorbent Assay ◽  
Dot Blot ◽  
Alveolar Epithelial ◽  
Dose Dependent

Objective. Paraquat (PQ), a widely used toxic herbicide, induces lung inflammation through mechanisms that remain incompletely understood. In a previous study, we found that the plasma MUC5B mucin level was implicated in PQ poisoning in patients. Here, we hypothesize that MUC5B is a critical mediator in PQ-induced cell inflammation. Methods. A mouse model of PQ-induced lung injury was used to examine the MUC5B expression level. A549 cells (alveolar epithelial cells line) were exposed to PQ in dose-dependent and time-dependent manners. Cell viability was detected by CCK-8 assays. The expression levels of MUC5B were examined by dot blot enzyme-linked immunosorbent assay (ELISA) and RT-qPCR. Western blotting was used to detect the levels of proteins in the MAPK and NF-κB pathways. Inflammatory factors in the cell culture medium were measured by ELISA. NF-κB and MAPK pathway inhibitors and MUC5B siRNA (siMUC5B) were used to determine the function of MUC5B. Finally, N-acetyl-cysteine (NAC) was added and its regulatory effect on the MAPK-NF-κB-MUC5B pathway was examined in PQ-induced cell inflammation. Results. MUC5B was significantly upregulated accompanying the increases in TNF-α and IL-6 secretion following PQ treatment in mouse and also in A549 cells after treatment with 50 μM PQ at 24 hours. Furthermore, MAPK and NF-κB pathway inhibitors could dramatically decrease the expression of MUC5B and the secretion of TNF-α and IL-6. Importantly, siMUC5B could significantly attenuate the secretion of TNF-α and IL-6 induced by PQ. As expected, the addition of NAC efficiently suppresses the TNF-α and IL-6 secretion stimulated from PQ and also downregulated ERK, JNK, and p65 phosphorylation (ERK/JNK MAPK and NF-κB pathways) as well as MUC5B expression. Conclusion. Our findings suggest that MUC5B participates in the process of PQ-induced cell inflammation and is downstream of the NF-κB and MAPK pathways. NAC can attenuate PQ-induced cell inflammation at least in part by suppressing the MAPK-NF-κB-MUC5B pathway. These results nominate MUC5B as a new biomarker and therapeutic target for PQ-induced lung inflammation.

scholarly journals α1-AMP-Activated Protein Kinase Regulates Hypoxia-Induced Na,K-ATPase Endocytosis via Direct Phosphorylation of Protein Kinase Cζ

2009 ◽  
Vol 29 (13) ◽  
pp. 3455-3464 ◽  
Author(s):  
Galina A. Gusarova ◽  
Laura A. Dada ◽  
Aileen M. Kelly ◽  
Chaya Brodie ◽  
Lee A. Witters ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Epithelial Cells ◽  
A549 Cells ◽  
Dominant Negative ◽  
Alveolar Epithelial Cells ◽  
Ampk Activation ◽  
Α Subunit ◽  
Alveolar Epithelial ◽  
Mitochondrial Ros ◽  
Amp Activated Protein Kinase

ABSTRACT Hypoxia promotes Na,K-ATPase endocytosis via protein kinase Cζ (PKCζ)-mediated phosphorylation of the Na,K-ATPase α subunit. Here, we report that hypoxia leads to the phosphorylation of 5′-AMP-activated protein kinase (AMPK) at Thr172 in rat alveolar epithelial cells. The overexpression of a dominant-negative AMPK α subunit (AMPK-DN) construct prevented the hypoxia-induced endocytosis of Na,K-ATPase. The overexpression of the reactive oxygen species (ROS) scavenger catalase prevented hypoxia-induced AMPK activation. Moreover, hypoxia failed to activate AMPK in mitochondrion-deficient ρ0-A549 cells, suggesting that mitochondrial ROS play an essential role in hypoxia-induced AMPK activation. Hypoxia-induced PKCζ translocation to the plasma membrane and phosphorylation at Thr410 were prevented by the pharmacological inhibition of AMPK or by the overexpression of the AMPK-DN construct. We found that AMPK α phosphorylates PKCζ on residue Thr410 within the PKCζ activation loop. Importantly, the activation of AMPK α was necessary for hypoxia-induced AMPK-PKCζ binding in alveolar epithelial cells. The overexpression of T410A mutant PKCζ prevented hypoxia-induced Na,K-ATPase endocytosis, confirming that PKCζ Thr410 phosphorylation is essential for this process. PKCζ activation by AMPK is isoform specific, as small interfering RNA targeting the α1 but not the α2 catalytic subunit prevented PKCζ activation. Accordingly, we provide the first evidence that hypoxia-generated mitochondrial ROS lead to the activation of the AMPK α1 isoform, which binds and directly phosphorylates PKCζ at Thr410, thereby promoting Na,K-ATPase endocytosis.

scholarly journals Antipseudomonal and Immunomodulatory Properties of Esc Peptides: Promising Features for Treatment of Chronic Infectious Diseases and Inflammation

2021 ◽  
Vol 22 (2) ◽  
pp. 557
Author(s):  
Floriana Cappiello ◽  
Veronica Carnicelli ◽  
Bruno Casciaro ◽  
Maria Luisa Mangoni
Keyword(s):  
Epithelial Cells ◽  
Infectious Diseases ◽  
Wound Repair ◽  
Alveolar Epithelial Cells ◽  
Enzyme Linked Immunosorbent Assay ◽  
Negative Bacterium ◽  
Scratch Assay ◽  
Alveolar Epithelial ◽  
Persistent Infections ◽  
Lung Tissue Damage

Persistent infections, such as those provoked by the Gram-negative bacterium Pseudomonas aeruginosa in the lungs of cystic fibrosis (CF) patients, can induce inflammation with lung tissue damage and progressive alteration of respiratory function. Therefore, compounds having both antimicrobial and immunomodulatory activities are certainly of great advantage in fighting infectious diseases and chronic inflammation. We recently demonstrated the potent antipseudomonal efficacy of the antimicrobial peptide (AMP) Esc(1-21) and its diastereomer Esc(1-21)-1c, namely Esc peptides. Here, we confirmed this antimicrobial activity by reporting on the peptides’ ability to kill P. aeruginosa once internalized into alveolar epithelial cells. Furthermore, by means of enzyme-linked immunosorbent assay and Western blot analyses, we investigated the peptides’ ability to detoxify the bacterial lipopolysaccharide (LPS) by studying their effects on the secretion of the pro-inflammatory cytokine IL-6 as well as on the expression of cyclooxygenase-2 from macrophages activated by P. aeruginosa LPS. In addition, by a modified scratch assay we showed that both AMPs are able to stimulate the closure of a gap produced in alveolar epithelial cells when cell migration is inhibited by concentrations of Pseudomonas LPS that mimic lung infection conditions, suggesting a peptide-induced airway wound repair. Overall, these results have highlighted the two Esc peptides as valuable candidates for the development of new multifunctional therapeutics for treatment of chronic infectious disease and inflammation, as found in CF patients.

scholarly journals Cysteine proteinases in bronchoalveolar epithelial cells and lavage fluid of rat lung.

1991 ◽  
Vol 39 (4) ◽  
pp. 461-468 ◽  
Author(s):  
Y Ishii ◽  
Y Hashizume ◽  
T Watanabe ◽  
S Waguri ◽  
N Sato ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Alveolar Macrophages ◽  
Cathepsin B ◽  
Light And Electron Microscopy ◽  
Lavage Fluid ◽  
Alveolar Epithelial Cells ◽  
Type Ii ◽  
Mature Form ◽  
Alveolar Epithelial ◽  
Cathepsin H

We examined the presence of cathepsins B, H, and L in bronchoalveolar epithelial cells, including alveolar macrophages, and in bronchoalveolar lavage fluid (BALF), using immunocytochemistry and immunoblotting. By light and electron microscopy, immunoreactivity for cathepsins B, H, and L was detected in lysosomes of ciliated and non-ciliated epithelial cells of bronchi and bronchioles, and in macrophages. Immunodeposits for cathepsin H only were demonstrated in lamellar bodies of Type II alveolar epithelial cells, suggesting the cosecretion of surfactants and cathepsin H from the cells into the alveolar space. By immunoblotting, cathepsins B and H were found to be present in BALF. To further investigate the origin of these enzymes in BALF, alveolar macrophages obtained from BALF were cultured for 6 hr in a serum-free medium. Immunoblotting revealed that protein bands corresponding to the pro-form and mature form of cathepsin B and the mature form of cathepsin H were present in the culture medium. From these results, the presence of cathepsins B and H in BALF can be explained by the fact that cathepsin B is secreted from alveolar macrophages and cathepsin H is secreted mainly with surfactants from Type II cells and also from macrophages.

scholarly journals Methemoglobin-induced signaling and chemokine responses in human alveolar epithelial cells

2014 ◽  
Vol 306 (1) ◽  
pp. L88-L100 ◽  
Author(s):  
Sharon Mumby ◽  
Latha Ramakrishnan ◽  
Timothy W. Evans ◽  
Mark J. D. Griffiths ◽  
Gregory J. Quinlan
Keyword(s):  
Epithelial Cells ◽  
Primary Cultures ◽  
A549 Cells ◽  
Alveolar Epithelial Cells ◽  
Lung Epithelial Cells ◽  
Alveolar Type ◽  
Alveolar Epithelial ◽  
Pathway Activation ◽  
Jnk Activation ◽  
Human Alveolar Epithelial Cells

Diffuse alveolar hemorrhage is characterized by the presence of red blood cells and free hemoglobin in the alveoli and complicates a number of serious medical and surgical lung conditions including the pulmonary vasculitides and acute respiratory distress syndrome. In this study we investigated the hypothesis that exposure of human alveolar epithelial cells to hemoglobin and its breakdown products regulates chemokine release via iron- and oxidant-mediated activation of the transcription factor NF-κB. Methemoglobin alone stimulated the release of IL-8 and MCP-1 from A549 cells via activation of the NF-κB pathway; additionally, IL-8 required ERK activation and MCP-1 required JNK activation. Neither antioxidants nor iron chelators and knockdown of ferritin heavy and light chains affected these responses, indicating that iron and reactive oxygen species are not involved in the response of alveolar epithelial cells to methemoglobin. Incubation of primary cultures of human alveolar type 2 cells with methemoglobin resulted in a similar pattern of chemokine release and signaling pathway activation. In summary, we have shown for the first time that methemoglobin induced chemokine release from human lung epithelial cells independent of iron- and redox-mediated signaling involving the activation of the NF-κB and MAPK pathways. Decompartmentalization of hemoglobin may be a significant proinflammatory stimulus in a variety of lung diseases.

Hypoxia upregulates VEGF expression in alveolar epithelial cells in vitro and in vivo

2002 ◽  
Vol 283 (5) ◽  
pp. L1133-L1142 ◽  
Author(s):  
Isabelle Pham ◽  
Tokujiro Uchida ◽  
Carole Planes ◽  
Lorraine B. Ware ◽  
Robert Kaner ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Bronchoalveolar Lavage Fluid ◽  
Lavage Fluid ◽  
Alveolar Epithelial Cells ◽  
Oxygen Species ◽  
Vegf Expression ◽  
Vegf Mrna ◽  
Alveolar Epithelial ◽  
Vegf Protein

We investigated regulation of vascular endothelial growth factor (VEGF) expression by hypoxia in cultured and freshly isolated rat alveolar epithelial cells (AEC). In vitro, hypoxia increased VEGF mRNA and protein levels, with maximal stimulation at 0% O2 for 18 h. A similar upregulation of VEGF expression was found in alveolar epithelial type II (ATII) cells freshly isolated from rats exposed to 8% O2 for 24 h. In vitro , hypoxia-induced upregulation of VEGF mRNA was due to an increase in transcription, rather than an increase in RNA stability, inasmuch as the half-life of VEGF mRNA was unchanged. Upregulation of VEGF mRNA by hypoxia was mimicked by CoCl2 and desferrioxamine in normoxic AEC and was not prevented by inhibitors of reactive oxygen species, suggesting that hypoxic VEGF regulation involved an O2-dependent protein that requires ferrous ions but is independent of reactive oxygen species generation. In polarized ATII cells, VEGF protein was secreted at the apical and basolateral sides. Similarly, in rats, VEGF was secreted in bronchoalveolar lavage fluid. Hypoxia induced a twofold increase in VEGF protein at the apical side of ATII cells in culture and in bronchoalveolar lavage fluid. These findings suggest that release of VEGF synthesized by AEC may target not only endothelial cells but also other alveolar cells, including macrophages and epithelial cells.

scholarly journals Aesculetin Attenuates Alveolar Injury and Fibrosis Induced by Close Contact of Alveolar Epithelial Cells with Blood-Derived Macrophages via IL-8 Signaling

2020 ◽  
Vol 21 (15) ◽  
pp. 5518
Author(s):  
Su Yeon Oh ◽  
Yun-Ho Kim ◽  
Min-Kyung Kang ◽  
Eun-Jung Lee ◽  
Dong Yeon Kim ◽  
...  
Keyword(s):  
Pulmonary Fibrosis ◽  
Close Contact ◽  
A549 Cells ◽  
Fold Increase ◽  
Lavage Fluid ◽  
Alveolar Epithelial Cells ◽  
Barrier Disruption ◽  
Alveolar Epithelial ◽  
Fold Induction ◽  
Factor Α

Pulmonary fibrosis is a disease in which lung tissues become fibrous and thereby causes severe respiratory disturbances. Various stimuli induce infiltration of macrophages to the respiratory tract, secreting inflammatory cytokines, which subsequently leads to the development of pulmonary fibrosis. Aesculetin, a major component of the sancho tree and chicory, is known to biologically have antioxidant and anti-inflammatory effects. Human alveolar epithelial A549 cells were cultured for 24 h in conditioned media of THP-1 monocyte-derived macrophages (mCM) with 1–20 μM aesculetin. Micromolar aesculetin attenuated the cytotoxicity of mCM containing inflammatory tumor necrosis factor-α (TNF)-α and interleukin (IL)-8 as major cytokines. Aesculetin inhibited alveolar epithelial induction of the mesenchymal markers in mCM-exposed/IL-8-loaded A549 cells (≈47–51% inhibition), while epithelial markers were induced in aesculetin-treated cells subject to mCM/IL-8 (≈1.5–2.3-fold induction). Aesculetin added to mCM-stimulated A549 cells abrogated the collagen production and alveolar epithelial CXC-chemokine receptor 2 (CXCR2) induction. The production of matrix metalloproteinase (MMP) proteins in mCM-loaded A549 cells was reduced by aesculetin (≈52% reduction), in parallel with its increase in tissue inhibitor of metalloproteinases (TIMP) proteins (≈1.8-fold increase). In addition, aesculetin enhanced epithelial induction of tight junction proteins in mCM-/IL-8-exposed cells (≈2.3–2.5-fold induction). The inhalation of polyhexamethylene guanidine (PHMG) in mice accompanied neutrophil predominance in bronchoalveolar lavage fluid (BALF) and macrophage infiltration in alveoli, which was inhibited by orally administrating aesculetin to mice. Treating aesculetin to mice alleviated PHMG-induced IL-8-mediated subepithelial fibrosis and airway barrier disruption. Taken together, aesculetin may antagonize pulmonary fibrosis and alveolar epithelial barrier disruption stimulated by the infiltration of monocyte-derived macrophages, which is typical of PHMG toxicity, involving interaction of IL-8 and CXCR2. Aesculetin maybe a promising agent counteracting macrophage-mediated inflammation-associated pulmonary disorders.

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