Inflammation In Lung Cells Research Articles

Dexamethasone, Remdesivir and Azithromycin modulate ACE2 and IL-6 in Lung Epithelial Cells.

The optimal use of steroids in COVID-19 patients remains challenging. Current S3-guidelines "Recommendations for patients with COVID-19" recommend dexamethasone (DEX) for patients requiring respiratory support, remdesivir (RD) in the early disease phase and azythromycin (AZ) is no longer recommended. We investigated effects of DEX, RD and AZ in a lipopolysaccharide induced inflammation in lung cells in vitro and analyzed publicly available datasets with a focus on the Angiotensin-converting enzyme 2 (ACE2) to better understand drugs' mechanisms of action. human bronchial (Calu) and alveolar (A549) lung epithelial cells were treated with DEX, AZ or RDV in the presence of lipopolysaccharides (LPS). Gene expression (GE) of ACE2, IL-6 and the IL-6 protein release were measured. Publicly available GE data from lung tissues of COVID-19 patients and from lung cells treated with DEX were analyzed for the GE of ACE2. DEX increased and RDV and AZ reduced the GE of ACE2 in LPS-stimulated bronchial and alveolar epithelial cells. Only DEX significantly reduced LPS-induced IL-6 releases in alveolar cells substantially. The database analyses showed an, albeit not always significant, increase in ACE2 for lung tissue or cell lines treated with DEX. Lung tissue from patients after COVID-19 infection as well as bronchial cell cultures after COVID-19 infection showed lower GEs of ACE2. DEX can increase ACE2 expression in vitro and thereby the portal of entry of SARS-CoV-2 into lung cells during an LPS induced inflammation. Simultaneously the inflammatory marker IL-6 is reduced. Comparative database analyses indicate that these processes can also take place in vivo.

Protective Effects of Proanthocyanidin-Rich Fraction from Red Rice Germ and Bran on Lung Cell Inflammation via Inhibition of NF-κB/NLRP3 Inflammasome Pathway.

The activation of the NLRP3 inflammasome pathway during infectious pathogen-induced immunopathology can lead to chronic inflammation and various adverse health outcomes. Identification of functional foods with anti-inflammatory properties is crucial for preventing inflammation triggered by NLRP3 inflammasome activation. This study aimed to investigate the anti-inflammatory properties of a proanthocyanidin-rich fraction obtained from red rice germ and bran against lipopolysaccharide (LPS) and adenosine triphosphate (ATP)-induced condition in A549 lung cells. The proanthocyanidin-rich fraction from Yamuechaebia 3 red rice extract (YM3-PRF) was obtained using column chromatography with Sephadex LH20, and its total proanthocyanidin content was determined to be 351.43 ± 1.18 mg/g extract using the vanillin assay. A549 lung cells were pretreated with YM3-PRF at concentrations of 5-20 μg/mL prior to exposure to LPS (1 μg/mL) and ATP (5 nM). The results showed that YM3-PRF significantly inhibited the expression of inflammatory mRNAs (NLRP3, IL-6, IL-1β, and IL-18) and the secretion of cytokines (IL-6, IL-1β, and IL-18) in a dose-dependent manner (p < 0.05). Mechanistically, YM3-PRF exerted its anti-inflammatory effects by inhibiting NF-κB translocation and downregulating proteins associated with the NLRP3 inflammasome pathway (NLRP3, ASC, pro-caspase-1, and cleaved-caspase-1). These findings suggest that the proanthocyanidin-rich fraction from red rice germ and bran has protective effects and may serve as a potential therapeutic option for chronic inflammatory diseases associated with NLRP3 inflammasome activation.

Isolation, Characterization, and Anti-Idiopathic Pulmonary Fibrosis Activity of a Fucoidan from Costaria costata.

Pulmonary fibrosis is a chronic, progressive, and fatal disease of the interstitial lung. There is currently a lack of efficient therapy to reverse the prognosis of patients. In this study, a fucoidan from Costaria costata was isolated, and its anti-idiopathic fibrosis activity was investigated both in vitro and in vivo. The chemical composition analysis showed that C. costata polysaccharide (CCP) consists of galactose and fucose as the main monosaccharides with a sulfate group content of 18.54%. Further study found that CCP could resist TGF-β1-induced epithelial-mesenchymal transition (EMT) in A549 cells by inhibiting the TGF-β/Smad and PI3K/AKT/mTOR signaling pathways. Moreover, in vivo study found that CCP treatment alleviated bleomycin (BLM)-stimulated fibrosis and inflammation in mice lung tissue. In conclusion, the present study suggests that CCP could protect the lung from fibrosis by relieving the EMT process and inflammation in lung cells.

Perfluoroalkyl Substances (PFAS) Affect Inflammation in Lung Cells and Tissues.

Adverse lung outcomes from exposure to per-and polyfluoroalkyl substances (PFAS) are known; however, the mechanism of action is poorly understood. To explore this, human bronchial epithelial cells were grown and exposed to varied concentrations of short-chain (perfluorobutanoic acid, perflurobutane sulfonic acid and GenX) or long-chain (PFOA and perfluorooctane sulfonic acid (PFOS)) PFAS, alone or in a mixture to identify cytotoxic concentrations. Non-cytotoxic concentrations of PFAS from this experiment were selected to assess NLRP3 inflammasome activation and priming. We found that PFOA and PFOS alone or in a mixture primed and activated the inflammasome compared with vehicle control. Atomic force microscopy showed that PFOA but not PFOS significantly altered the membrane properties of cells. RNA sequencing was performed on the lungs of mice that had consumed PFOA in drinking water for 14 weeks. Wild type (WT), PPARα knock-out (KO) and humanized PPARα (KI) were exposed to PFOA. We found that multiple inflammation- and immune-related genes were affected. Taken together, our study demonstrated that PFAS exposure could alter lung biology in a significant manner and may contribute to asthma/airway hyper-responsiveness.

A Correlation among the COVID-19 Spread, Particulate Matters, and Angiotensin-Converting Enzyme 2: A Review.

Air pollution (AP) is one of the leading causes of health risks because it causes widespread morbidity and mortality every year. Its impact on the environment includes acid rain and decreased visibility, but more importantly, it also has an impact on human health. The rise of COVID-19 demonstrates the cost of failing to manage AP. COVID-19 can be spread through the air, and atmospheric particulate matters (PMs) can create a good atmosphere for the long-distance spread of the virus. Moreover, these PMs can cause lung cell inflammation, thereby increasing sensitivity and the severity of symptoms in COVID-19 patients. In this study, we emphasized the potential role of PMs in the spread of COVID-19. The relationship among COVID-19, PMs, and angiotensin-converting enzyme 2 (ACE2) (receptor involved in virus entry into lung cells and inflammation) was also summarized.

Air Pollution and Covid-19: The Role of Particulate Matter in the Spread and Increase of Covid-19's Morbidity and Mortality.

Sars-Cov-2 virus (COVID-19) is a member of the coronavirus family and is responsible for the pandemic recently declared by the World Health Organization. A positive correlation has been observed between the spread of the virus and air pollution, one of the greatest challenges of our millennium. COVID-19 could have an air transmission and atmospheric particulate matter (PM) could create a suitable environment for transporting the virus at greater distances than those considered for close contact. Moreover, PM induces inflammation in lung cells and exposure to PM could increase the susceptibility and severity of the COVID-19 patient symptoms. The new coronavirus has been shown to trigger an inflammatory storm that would be sustained in the case of pre-exposure to polluting agents. In this review, we highlight the potential role of PM in the spread of COVID-19, focusing on Italian cities whose PM daily concentrations were found to be higher than the annual average allowed during the months preceding the epidemic. Furthermore, we analyze the positive correlation between the virus spread, PM, and angiotensin-converting enzyme 2 (ACE2), a receptor involved in the entry of the virus into pulmonary cells and inflammation.

Induction of antioxidant mechanisms in lung during experimental pancreatitis in rats

Lung complications are the most common cause of death in patients with acute pancreatitis. In this study, we investigated how induction of mild acute pancreatitis could modify the course of lung inflammation, eventually, induced by a severe acute pancreatitis in rats. A severe and a mild forms of an experimental acute pancreatitis were respectively established by intra-ductal administration of sodium taurocholate to final dose of 50 mg/kg body wt. and intra-peritoneal injection of caerulein to supramaximal dose of 40 mg/kg body wt. We observed reduced levels of thiobarbiturate acid reacting substances when severe pancreatitis was preceded by the induction of mild pancreatitis. Moreover, mRNAs expression of both HSP-70 and Mn-SOD was increased in the lung. By contrast, the level of glutathione was reduced, but no change in the infiltration of neutrophils was observed. Therefore, we conclude that during the course of pancreatitis and its related lung inflammation, the pulmonary cells response involved in the expression of different protective proteins, including HSP-70 and Mn-SOD, which possibly improves the defensive mechanisms against inflammation in lung cells

Silicon‐based quantum dots induce inflammation in human lung cells and disrupt extracellular matrix homeostasis

Quantum dots (QDs) are nanocrystalline semiconductor materials that have been tested for biological applications such as cancer therapy, cellular imaging and drug delivery, despite the serious lack of information of their effects on mammalian cells. The present study aimed to evaluate the potential of Si/SiO2 QDs to induce an inflammatory response in MRC-5 human lung fibroblasts. Cells were exposed to different concentrations of Si/SiO2 QDs (25-200 μg·mL(-1)) for 24, 48, 72 and 96 h. The results obtained showed that uptake of QDs was dependent on biocorona formation and the stability of nanoparticles in various biological media (minimum essential medium without or with 10% fetal bovine serum). The cell membrane damage indicated by the increase in lactate dehydrogenase release after exposure to QDs was dose- and time-dependent. The level of lysosomes increased proportionally with the concentration of QDs, whereas an accumulation of autophagosomes was also observed. Cellular morphology was affected, as shown by the disruption of actin filaments. The enhanced release of nitric oxide and the increase in interleukin-6 and interleukin-8 protein expression suggested that nanoparticles triggered an inflammatory response in MRC-5 cells. QDs decreased the protein expression and enzymatic activity of matrix metalloproteinase (MMP)-2 and MMP-9 and also MMP-1 caseinase activity, whereas the protein levels of MMP-1 and tissue inhibitor of metalloproteinase-1 increased. The present study reveals for the first time that silicon-based QDs are able to generate inflammation in lung cells and cause an imbalance in extracellular matrix turnover through a differential regulation of MMPs and tissue inhibitor of metalloproteinase-1 protein expression.

Evidence for Proinflammatory β-1,6 Glucans in the Pneumocystis carinii Cell Wall.

Inflammation is a major cause of respiratory impairment during Pneumocystis pneumonia. Studies support a significant role for cell wall β-glucans in stimulating inflammatory responses. Fungal β-glucans are comprised of d-glucose homopolymers containing β-1,3-linked glucose backbones with β-1,6-linked glucose side chains. Prior studies in Pneumocystis carinii have characterized β-1,3 glucan components of the organism. However, recent investigations in other organisms support important roles for β-1,6 glucans, predominantly in mediating host cellular activation. Accordingly, we sought to characterize β-1,6 glucans in the cell wall of Pneumocystis and to establish their activity in lung cell inflammation. Immune staining revealed specific β-1,6 localization in P. carinii cyst walls. Homology-based cloning facilitated characterization of a functional P. carinii kre6 (Pckre6) β-1,6 glucan synthase in Pneumocystis that, when expressed in kre6-deficient Saccharomyces cerevisiae, restored cell wall stability. Recently synthesized β-1,6 glucan synthase inhibitors decreased the ability of isolated P. carinii preparations to generate β-1,6 carbohydrate. In addition, isolated β-1,6 glucan fractions from Pneumocystis elicited vigorous tumor necrosis factor alpha (TNF-α) responses from macrophages. These inflammatory responses were significantly dampened by inhibition of host cell plasma membrane microdomain function. Together, these studies indicate that β-1,6 glucans are present in the P. carinii cell wall and contribute to lung cell inflammatory activation during infection.

Asthma Drugs Counter-regulate interleukin-8 Release Stimulated by Sodium Sulfite in an A549 Cell Line

Background. Clinical manifestations suggest that air pollution may induce deterioration of respiratory health. Some air pollutants, including sulfite, may play a role in the exacerbation of asthma. Sulfites are formed at bronchial mucosa from inhaled sulfur dioxide. It has been previously reported that sodium sulfite (Na2SO3) has pro-inflammatory properties and enhances neutrophil adhesion to A549 cells. Interleukin-8 (IL-8) plays a critical role in attracting inflammatory cells and is an excellent marker of pulmonary cell activation. To date, there have not been any reports on the effect of asthma drugs on the suppression of IL-8 production induced by sulfite in A549 cells or the involvement of specific signal transduction pathways. Thus, our study assessed the effects of salmeterol, fluticasone, and montelukast on human epithelial lung cell inflammation as well as the inhibitors in different signal transduction pathways. Methods. A549 human lung epithelial cells were cultured under the following conditions: (1) treated with sodium sulfite (0, 100, 500, 1000, 2500 uM) for 16 hours; (2) cultured for 1 hour in the presence of SB203580, PD98059, SP600125, or wedeloactone, then co-incubated with sodium sulfite for another 16 hours; (3) cultured for 4 hours in the presence of salmeterol, fluticasone, or montelukast, then stimulated with sodium sulfite at a concentration of 1000 uM for 16 hours. We collected the supernatants from the above conditions and performed enzyme-linked immunosorbent assay (ELISA) to measure the IL-8 concentration. Results. IL-8 production increased after treatment with sodium sulfite at 1000 to 2500 uM (p ≤ 0.001). SB203580, PD98059, and wedeloactone decreased IL-8 production stimulated by Na2SO3 (p < 0.01). Salmeterol, fluticasone, and montelukast significantly suppressed IL-8 secretion from sodium sulfite-stimulated A549 cells (p < 0.01). Conclusions. Sodium sulfite has pro-inflammatory properties in vitro and can induce potent chemotactic factor IL-8 production. Possible signal transduction pathways required for IL-8 gene expression following exposure to sulfite are the NF-κ B, ERK, and p-38-dependent pathways. Salmeterol, fluticasone, and montelukast all have inhibitory effects on sodium sulfite-induced IL-8 production in A549 cells.