Chicoric acid alleviates LPS-induced inflammatory response through miR-130a-3p/IGF-1pathway in human lung A549 epithelial cells

To investigate the effects and potential mechanisms of chicoric acid (CA) on LPS-induced inflammatory response in A549 cells. 0–800 μM CA was added to A549 cells to determine the toxicity of CA using MTT assay. Then, 2 μg/mL LPS and 50 μM CA were simultaneously added to A549 cells to investigate the effects of CA. In order to investigate the effects of miR-130a-3p and IGF-1 on LPS-induced A549 cells, cells were infected with inhibitor of miR-130a-3p and si RNA IGF-1. The levels of inflammatory cytokines such as IL-1β, IL-6, and TNF-α were measured by real-time RT-PCR and enzyme-linked immunosorbent (ELISA) assay. The IGF-1 pathway and NF-κB expression were measured using immunoblot assay. Moreover, a luciferase activity assay was used to indicate the binding site of miR-130a-3p on the 3′UTR of IGF-1. 0–50 μM CA had no toxicity on A549 cells. Thus, we chose 50 μM CA for the following study. CA attenuated the inflammatory response by LPS through decreasing IL-1β, IL-6, and TNF-α levels and increasing IGF-1/IGF-1R expression. Inhibition of miR-130a-3p reduced the inflammatory response and restored IGF-1/IGF-1R pathway induced by LPS. Furthermore, luciferase activity results indicated that miR-130a-3p directly targeted IGF-1 to regulate inflammatory response. CA alleviates LPS-induced inflammatory response through miR-130a-3p/IGF-1pathway in A549 cells.

Download Full-text

Dexamethasone can attenuate the pulmonary inflammatory response via regulation of the lncH19/miR-324-3p cascade

10.21203/rs.2.22494/v3 ◽

2020 ◽

Author(s):

Ye Chen ◽

Chao Zhang ◽

Changxue Xiao ◽

Xiao-dong Li ◽

Zhi-li Hu ◽

...

Keyword(s):

Cell Proliferation ◽

Inflammatory Response ◽

Inflammatory Cytokines ◽

Cell Apoptosis ◽

Cell Model ◽

A549 Cells ◽

Rt Pcr ◽

Function Study ◽

Tnf Α ◽

Pulmonary Inflammatory Response

Abstract Objective: To investigate lncRNAs and their roles in regulating the pulmonary inflammatory response under treatment of Dexamethasone (Dex).Methods: IL-1β (10 ng/mL) and LPS (1 μg/mL) was used to induce an inflammatory cell model with A549 cells, and the results showed that IL-1β performed better against LPS. Dex with different concentration was used to attenuate inflammation by IL-1β, and its effect was assessed by RT-PCR to detect the inflammatory related mRNA, including IKβ-α, IKKβ, IL-6, IL-8, and TNF-α. And ELISA to detect the inflammatory cytokines TNF-α, IL-6 and IL-8. RT-PCR was used to quantify levels of lncRNAs, including lncMALAT1, lncHotair, lncH19, and lncNeat1. LncH19 was most closely correlated with the inflammatory response, which was induced by IL-1β and attenuated by Dex. Among the lncRNAs, the level of lncH19 exhibited the highest increase following treatment with 1 μM and 10 μM Dex. Therefore, lncH19 was selected for further function study. LncH19 expression was inhibited by shRNA transduced by lentivirus. Cell assays for cell proliferation and apoptosis as well as RT-PCR, western blot, and ELISA for inflammatory related genes were conducted to confirm the functions of lncH19. Predicted target miRNAs of lncH19 included the following: hsa-miR-346, hsa-miR-324-3p, hsa-miR-18a-3p, hsa-miR-18b-5p, hsa-miR-146b-3p, hsa-miR-19b-3p and hsa-miR-19a-3p. Following estimation by RT-PCR, hsa-miR-346, hsa-miR-18a-3p and hsa-miR-324-3p showed consistent patterns in A549 NC and A549 shlncH19. miRNA inhibitor was transfected into A549 NC and A549 shlncH19cells, and expression levels were determined by RT-PCR. Hsa-miR-324-3p was inhibited the most relative to hsa-miR-346 and hsa-miR-18a-3p and was subjected to further function study. RT-PCR, ELISA and western blotting for inflammatory related genes detection were conducted to validate the functions of the target hsa-miR-324-3p.Results: Dex with 1 μM and 10 μM were shown to be effective in attenuating the inflammatory response. During this process, lncH19 significantly increased in expression (P < 0.05). Dex with 1 μM was for further study. Under IL-1β treatment with or without Dex, the inhibition of lncH19 lead to an increase cell proliferation, a decrease in cell apoptosis, an increase in the protein level of inflammatory-related genes, the phosphorylation of P65, ICAM-1 and VCAM-1, and inflammatory cytokines. Following prediction of the targets of lncH19 and validation by RT-PCR, miR-346, miR-18a-3p and miR-324-3p were found to be negatively correlated to lncH19. Additionally, Dex increased the expression of lncH19, but the expression of the miRNAs was reduced. Among miRNAs, miR-324-3p was the most markedly down-regulated following treatment of miRNA inhibitors. The MTS assay and cell apoptosis assay showed that the miR-324-3p inhibitor inhibited cell proliferation and induced cell apoptosis, thereby significantly attenuating the inflammatory response, which reversed the effect of lncH19 in regulating cell proliferation and the secretion of inflammatory cytokines (P < 0.05). Therefore, lncH19 might regulate miR-324-3p during Dex treatment in pulmonary inflammatory response.Conclusion: Dex can attenuate the pulmonary inflammatory response via regulation of the lncH19/miR-324-3p cascade.

Download Full-text

Biological Evaluation of Alkyl Triphenylphosphonium Ostruthin Derivatives as Potential Anti-Inflammatory Agents Targeting the Nuclear Factor κB Signaling Pathway in Human Lung Adenocarcinoma A549 Cells

BioChem ◽

10.3390/biochem1020010 ◽

2021 ◽

Vol 1 (2) ◽

pp. 107-121

Author(s):

Nghia Trong Vo ◽

Eiichi Kusagawa ◽

Kaori Nakano ◽

Chihiro Moriwaki ◽

Yasunobu Miyake ◽

...

Keyword(s):

Lung Adenocarcinoma ◽

Signaling Pathway ◽

Human Lung ◽

A549 Cells ◽

Nuclear Factor Κb ◽

Nuclear Factor ◽

Human Lung Adenocarcinoma ◽

Tnf Α ◽

Anti Inflammatory ◽

Lung Adenocarcinoma A549

Ostruthin (6-geranyl-7-hydroxycoumarin) is one of the constituents isolated from Paramignya trimera and has been classified as a simple coumarin. We recently reported the synthesis of alkyl triphenylphosphonium (TPP) derivatives from ostruthin and evaluated their anticancer activities. In the present study, we demonstrated that alkyl TPP ostruthin derivatives inhibited the up-regulation of cell-surface intercellular adhesion molecule-1 (ICAM-1) in human lung adenocarcinoma A549 cells stimulated with tumor necrosis factor-α (TNF-α) without affecting cell viability, while ostruthin itself exerted cytotoxicity against A549 cells. The heptyl TPP ostruthin derivative (termed OS8) attenuated the up-regulation of ICAM-1 mRNA expression at concentrations higher than 40 µM in TNF-α-stimulated A549 cells. OS8 inhibited TNF-α-induced nuclear factor κB (NF-κB)-responsive luciferase reporter activity at concentrations higher than 40 µM, but did not affect the translocation of the NF-κB subunit RelA in response to the TNF-α stimulation at concentrations up to 100 µM. A chromatin immunoprecipitation assay showed that OS8 at 100 µM prevented the binding of RelA to the ICAM-1 promoter. We also showed that OS8 at 100 µM inhibited the TNF-α-induced phosphorylation of RelA at Ser 536. Moreover, the TNF-α-induced phosphorylation of an inhibitor of NF-κB α and extracellular signal-regulated kinase was reduced by OS8. These results indicate that OS8 has potential as an anti-inflammatory agent that targets the NF-κB signaling pathway.

Download Full-text

Anti-Inflammatory Effects of Neochlorogenic Acid Extract from Mulberry Leaf (Morus alba L.) Against LPS-Stimulated Inflammatory Response through Mediating the AMPK/Nrf2 Signaling Pathway in A549 Cells

Molecules ◽

10.3390/molecules25061385 ◽

2020 ◽

Vol 25 (6) ◽

pp. 1385 ◽

Cited By ~ 5

Author(s):

Xiao-han Gao ◽

Sun-dong Zhang ◽

Li-tao Wang ◽

Liang Yu ◽

Xue-lian Zhao ◽

...

Keyword(s):

Inflammatory Response ◽

Signaling Pathway ◽

A549 Cells ◽

Morus Alba ◽

Mulberry Leaf ◽

Tnf Α ◽

Nrf2 Signaling Pathway ◽

Acute Pneumonia ◽

Neochlorogenic Acid ◽

Anti Inflammatory

Neochlorogenic acid (nCGA) is a phenolic compound isolated from mulberry leaf (Morus alba L.), which possesses multiple pharmacological activities containing antioxidant and anti-inflammatory effects. However, the role of nCGA in the treatment of acute pneumonia and the underlying molecular mechanism are still unclear. Hence, the aim of study is to investigate the anti-inflammatory properties of nCGA on LPS-stimulated inflammation in A549 cells. In the present study, results reported that nCGA without cytotoxicity significantly reduced the production of TNF-α, IL-6, and NO, and further suppressed the proteins of iNOS, COX2, TNF-α, IL-6 expression. Furthermore, nCGA also inhibited NF-κB activation and blocked MAPKs signaling pathway phosphorylation. In addition, we found nCGA significantly increased the expression of HO-1 via activating the AMPK/Nrf2 signaling pathway to attenuate the inflammatory response, whereas this protective effect of nCGA was reversed by pre-treatment with compound C (C.C, an AMPK inhibitor). Therefore, all these results indicated that nCGA might act as a natural anti-inflammatory agent for the treatment of acute pneumonia.

Download Full-text

Enhancement of Cell Death by TNF α-related Apoptosis-inducing Ligand (TRAIL) in Human Lung Carcinoma A549 Cells Exposed to X Rays under Hypoxia

Journal of Radiation Research ◽

10.1269/jrr.07028 ◽

2007 ◽

Vol 48 (6) ◽

pp. 461-468 ◽

Cited By ~ 6

Author(s):

Momoko TAKAHASHI ◽

Osamu INANAMI ◽

Nobuo KUBOTA ◽

Michihiko TSUJITANI ◽

Hironobu YASUI ◽

...

Keyword(s):

Cell Death ◽

Lung Carcinoma ◽

Human Lung ◽

A549 Cells ◽

X Rays ◽

Tnf Α ◽

Human Lung Carcinoma

Download Full-text

Dexamethasone can attenuate the pulmonary inflammatory response via regulation of the lncH19/miR-324-3p cascade

Journal of Inflammation ◽

10.1186/s12950-020-00266-0 ◽

2021 ◽

Vol 18 (1) ◽

Author(s):

Ye Chen ◽

Chao Zhang ◽

Chang-xue Xiao ◽

Xiao-dong Li ◽

Zhi-li Hu ◽

...

Keyword(s):

Cell Proliferation ◽

Inflammatory Response ◽

Inflammatory Cytokines ◽

Cell Apoptosis ◽

Mrna Levels ◽

Rt Pcr ◽

Inflammatory Genes ◽

Functional Studies ◽

Tnf Α ◽

Pulmonary Inflammatory Response

Abstract Objective To investigate lncRNAs and their roles in regulating the pulmonary inflammatory response under dexamethasone (Dex) treatment. Methods IL-1β (10 ng/mL) and LPS (1 μg/mL) was used to construct inflammatory cell models with A549 cells; IL-1β performed better against LPS. Different concentrations of Dex were used to attenuate the inflammation induced by IL-1β, and its effect was assessed via RT-PCR to detect inflammatory cytokine-related mRNA levels, including those of IKβ-α, IKKβ, IL-6, IL-8, and TNF-α. Furthermore, ELISA was used to detect the levels of the inflammatory cytokines TNF-α, IL-6, and IL-8. RT-PCR was used to quantify the levels of lncRNAs, including lncMALAT1, lncHotair, lncH19, and lncNeat1. LncH19 was most closely associated with the inflammatory response, which was induced by IL-1β and attenuated by Dex. Among the lncRNAs, the level of lncH19 showed the highest increase following treatment with 1 and 10 μM Dex. Therefore, lncH19 was selected for further functional studies. LncH19 expression was inhibited by shRNA transduced with lentivirus. Cell assays for cell proliferation and apoptosis as well as RT-PCR, western blot, and ELISA for inflammatory genes were conducted to confirm the functions of lncH19. The predicted target miRNAs of lncH19 were hsa-miR-346, hsa-miR-324-3p, hsa-miR-18a-3p, hsa-miR-18b-5p, hsa-miR-146b-3p, hsa-miR-19b-3p, and hsa-miR-19a-3p. Following estimation via RT-PCR, hsa-miR-346, hsa-miR-18a-3p, and hsa-miR-324-3p showed consistent patterns in A549 NC and A549 shlncH19. An miRNA inhibitor was transfected into A549 NC and A549 shlncH19 cells, and the expression levels were determined via RT-PCR. hsa-miR-324-3p was inhibited the most compared with hsa-miR-346 and hsa-miR-18a-3p and was subjected to further functional studies. RT-PCR, ELISA, and western blotting for inflammatory gene detection were conducted to validate the functions of the target hsa-miR-324-3p. Results Treatment with 1 and 10 μM Dex could effectively attenuate the inflammatory response. During this process, lncH19 expression significantly increased (P < 0.05). Therefore, treatment with 1 μM Dex was used for further study. Under IL-1β treatment with or without Dex, lncH19 inhibition led to an increase in cell proliferation; a decrease in cell apoptosis; an increase in the protein levels of inflammatory genes; phosphorylation of P65, ICAM-1, and VCAM-1; and increase inflammatory cytokines. Prediction of the targets of lncH19 and validation via RT-PCR revealed that miR-346, miR-18a-3p, and miR-324-3p negatively correlate with lncH19. Additionally, Dex increased the lncH19 expression but reduced that of the miRNAs. Among the miRNAs, miR-324-3p was the most markedly downregulated miRNA following treatment of miRNA inhibitors. The MTS assay and cell apoptosis assay showed that the miR-324-3p inhibitor inhibited cell proliferation and induced cell apoptosis, thereby significantly attenuating the inflammatory response, which reversed the effect of lncH19 in regulating cell proliferation and the secretion of inflammatory cytokines (P < 0.05). Therefore, lncH19 might regulate miR-324-3p in pulmonary inflammatory response under Dex treatment. Conclusion Dex can attenuate the pulmonary inflammatory response by regulating the lncH19/miR-324-3p cascade.

Download Full-text

Paeoniflorin reduces the inflammatory response of THP-1 cells by up‐regulating microRNA-124

Genes & Genomics ◽

10.1007/s13258-021-01083-2 ◽

2021 ◽

Author(s):

Danyun Huang ◽

Zhijun Li ◽

Yue Chen ◽

Yan Fan ◽

Tao Yu

Keyword(s):

Systemic Lupus Erythematosus ◽

Flow Cytometry ◽

Inflammatory Response ◽

Inflammatory Cytokines ◽

Functional Recovery ◽

Lupus Erythematosus ◽

Biological Functions ◽

Rt Pcr ◽

Systemic Lupus ◽

Tnf Α

Abstract Background The activation of macrophages and the release of inflammatory cytokines are the main reasons for the progress of systemic lupus erythematosus (SLE). MicroRNA (miRNA)-124 is involved in the regulation of macrophages and is a key regulator of inflammation and immunity. Objective To explore whether paeoniflorin (PF) regulates the biological functions of macrophages depends on miR-124. Methods RT-PCR, WB, ELISA, CCK-8 and flow cytometry were used to evaluate that PF regulated the biological functions of THP-1 cells through miR-124. Results PF significantly inhibited the proliferation while promotes the apoptosis of THP-1 cells, and inhibited the release of IL-6, TNF-α and IL-1βin THP-1 cells. RT-PCR results shown that PF up-regulated the expression of miR-124 in THP-1 cells. Functional recovery experiments showed that compared with the LPS + mimic-NC group, LPS + miR-124 mimic significantly inhibited the proliferation and the release of IL-6, TNF-α and IL-1β, but promoted the apoptosis of THP-1 cells. In addition, compared with the LPS + PF + inhibitor-NC group, LPS + PF + miR-124 inhibitor significantly promoted the proliferation and the release of IL-6, TNF-α and IL-1β, but inhibited the apoptosis of THP-1 cells. Conclusions By down-regulating miR-124, PF inhibits the proliferation and inflammation of THP-1 cells, and promotes the apoptosis of THP-1 cells.

Download Full-text

Induction of Proinflammatory Cytokines in Human Lung Epithelial Cells during Chlamydia pneumoniae Infection

Infection and Immunity ◽

10.1128/iai.71.2.614-620.2003 ◽

2003 ◽

Vol 71 (2) ◽

pp. 614-620 ◽

Cited By ~ 40

Author(s):

Jun Yang ◽

W. Craig Hooper ◽

Donald J. Phillips ◽

Maria L. Tondella ◽

Deborah F. Talkington

Keyword(s):

Epithelial Cells ◽

Chlamydia Pneumoniae ◽

Human Lung ◽

A549 Cells ◽

Cytokine Response ◽

Lung Epithelial Cells ◽

Cytokine Gene Expression ◽

Cytokine Release ◽

Tnf Α ◽

Respiratory Epithelial

ABSTRACT Chlamydia pneumoniae is an obligate intracellular human pathogen that causes acute respiratory diseases such as pneumonia and bronchitis. Previous studies have established that C. pneumoniae can induce cytokines in mouse and/or human cells, but little information is available on the cytokine response of respiratory epithelial cells, a first line of infection. In this study, heparin treatment of C. pneumoniae significantly reduced its ability to induce interleukin 8 (IL-8) and tumor necrosis factor alpha (TNF-α) mRNA in human lung carcinoma cells, indicating that cytadherence is an important early stimulus for induction of proinflammatory mediators. Although the IL-8, gamma interferon, and TNF-α message was consistently induced by infection of A549 cells not treated with heparin, only an elevation of IL-8 protein was detected in A549 supernatants. A549 IL-β and IL-6 mRNA and supernatant protein profiles were not significantly changed by infection. Heat or UV inactivation of C. pneumoniae only partially reduced the cytokine response, and inhibition of C. pneumoniae protein or DNA synthesis did not affect its ability to induce cytokine gene expression. To prevent stress-induced cytokine release by the A549 cells, centrifugation was not utilized for infection experiments. These experiments establish the importance of cytadherence in cytokine release by cells of respiratory epithelial origin and suggest that further work in the area of cytokine mediators is warranted to gain valuable pathogenic and therapeutic insights.

Download Full-text

Dexamethasone can attenuate the inflammatory response in asthma via regulation of the lncH19/miR-324-3p cascade

10.21203/rs.2.22494/v2 ◽

2020 ◽

Author(s):

Ye Chen ◽

Chao Zhang ◽

Changxue Xiao ◽

Xiao-dong Li ◽

Zhi-li Hu ◽

...

Keyword(s):

Cell Proliferation ◽

Inflammatory Response ◽

Western Blot ◽

Inflammatory Cytokines ◽

Cell Apoptosis ◽

Cell Model ◽

A549 Cells ◽

Tnf Alpha ◽

Rt Pcr ◽

Function Study

Abstract Objective: To investigate lncRNAs and their roles in regulating the inflammatory response under treatment of Dexamethasone (Dex) in asthma.Methods: IL-1 beta (10 ng/ml) and LPS (1 μg/ml) was used to induce an inflammatory cell model with A549 cells, and the results showed that IL-1 beta performed better against LPS. Dex with different concentration was used to attenuate inflammation by IL-1 beta, and its effect was assessed by RT-PCR to detect the inflammatory related mRNA, including IKbeta-alpha, IKKbeta, IL-6, IL-8, and TNF-alpha and ELISA to detect the inflammatory cytokines TNF-alpha, IL-6 and IL-8. RT-PCR was used to quantify levels of lncRNAs, including lncMALAT1, lncHotair, lncH19, and lncNeat1. lncH19 was most closely correlated with the inflammatory response, which was induced by IL-1beta and attenuated by Dex, Among the lncRNAs, the level of lncH19 exhibited the highest increase following treatment with 1 μM and 10 μM Dex. Therefore, lncH19 was selected for further function study. lncH19 expression was inhibited by shRNA transduced by lentivirus. Cell assays for cell proliferation and apoptosis as well as RT-PCR, western blot, and ELISA for inflammatory related genes were conducted to confirm the functions of lncH19. Predicted target miRNAs of lncH19 included the following: hsa-miR-346, hsa-miR-324-3p, hsa-miR-18a-3p, hsa-miR-18b-5p, hsa-miR-146b-3p, hsa-miR-19b-3p, and hsa-miR-19a-3p. Following estimation by RT-PCR, hsa-miR-346, hsa-miR-18a-3p, hsa-miR-324-3p showed consistent patterns in A549 NC and A549 shlncH19. miRNA inhibitor was transfected into A549 NC and A549 shlncH19 cells, and expression levels were determined by RT-PCR. hsa-miR-324-3p was inhibited the most relative to hsa-miR-346 and hsa-miR-18a-3p and was subjected to further function study. RT-PCR, ELISA and Western Blot for inflammatory related genes detection were conducted to validate the functions of the target hsa-miR-324-3p. Results: Dex with 1μM and 10 μM were shown to be effective in attenuating the inflammatory response. During this process, lncH19 significantly increased in expression (P < 0.05). Dex with 1μM was for further study. Under IL-1 beta treatment with or without Dex, the inhibition of lncH19 lead to an increase cell proliferation, a decrease in cell apoptosis, an increase in the protein level of inflammatory-related genes, and the phosphorylation of P65, ICAM-1, VCAM-1, and inflammatory cytokines. Following prediction of the targets of lncH19 and validation by RT-PCR, miR-346, miR-18a-3p, and miR-324-3p were found to be negatively correlated to lncH19. Additionally, Dex increased the expression of lncH19, but the expression of the aforementioned miRNAs was reduced. Among miRNAs, miR-324-3p was the most markedly down-regulated following treatment of miRNA inhibitors. The MTS assay and cell apoptosis assay showed that the miR-324-3p inhibitor inhibited cell proliferation and induced cell apoptosis, thereby significantly attenuating the inflammatory response, which reversed the effect of lncH19 in regulating cell proliferation and the secretion of inflammatory cytokines (P < 0.05). Therefore, lncH19 might regulate miR-324-3p during Dex treatment in inflammatory response of asthma.Conclusion: Dex can attenuate the inflammatory response in asthma via regulation of the lncH19/miR-324-3p cascade.

Download Full-text

Nrf2 Alleviates TNF-α-Induced Oxidative Stress Damage in Type II Alveolar Epithelial Cells by Down-Regulating the Expression of NOX1

10.21203/rs.3.rs-68779/v1 ◽

2020 ◽

Author(s):

Weijing Wu ◽

Jiamin Zhang ◽

Xihua Lian ◽

Xiaoping Lin ◽

Xiaoshan Su ◽

...

Keyword(s):

Oxidative Stress ◽

Epithelial Cells ◽

Binding Site ◽

Luciferase Activity ◽

A549 Cells ◽

Alveolar Epithelial Cells ◽

Type Ii ◽

Alveolar Epithelial ◽

Tnf Α ◽

Stress Damage

Abstract Objective: To study the roles of Nrf2 in acute lung injury (ALI) pathogenesis by investigating the effects of Nrf2 on regulating oxidative stress damage in TNF-α-induced type II alveolar epithelial cells (T2AECs).Methods: T2AECs were transfected with Nrf2 siRNA and overexpression vectors for six hours before being induced by TNF-α for 24 hours. Subsequently, levels of interleukins (IL-6 and IL-8), reactive oxygen species (ROS), malondialdehyde (MDA), total antioxidation capability (T-AOC), Nrf2, NOX1 and NF-kB were measured. Additionally, potential Nrf2 binding site in NOX1 promoter was predicted by AliBaba2.1 and two recombinant vectors, namely “pGL3-NOX1-1500” and “pGL3-NOX1-1489, were constructed by inserting the sequence of NOX1 promoter in full-length and that in the absence of Nrf2 binding site to pGL3 basic vector. T2AECs were transfected with these vectors prior to TNF-α induction and the luciferase activity was measured.Results: Levels of IL-6, IL-8, ROS and MDA were increased (P＜0.05) while T-AOC was decreased in TNF-α-induced A549 cells after the transfection of Nrf2 siRNA vector (P＜0.05). In contrast, concentrations of IL-6, IL-8, ROS and MDA were decreased (P＜0.05) whereas T-AOC was increased after the transfection of Nrf2 overexpression vector (P＜0.05). NOX1 promoter possesses one Nrf2 binding site. Cells transfected by “pGL3-NOX1-1500” vector had the highest luciferase activity, followed by cells transfected by “pGL3-NOX1-1489” vector and the control cells (P＜0.05).Conclusion: Nrf2 modulates NOX1 expression via binding to its promoter, by which against TNF-α-induced oxidative stress damage in T2AECs. Thus, Nrf2 might be a therapeutic target for ALI.

Download Full-text

Combination Therapy With Polydeoxyribonucleotide and Pirfenidone Alleviates Symptoms of Acute Respiratory Distress Syndrome in Human Lung Epithelial A549 Cells

International Neurourology Journal ◽

10.5213/inj.2040152.076 ◽

2020 ◽

Vol 24 (Suppl 1) ◽

pp. S56-64 ◽

Cited By ~ 2

Author(s):

Jae-Joon Hwang ◽

Il-Gyu Ko ◽

Jun-Jang Jin ◽

Lakkyong Hwang ◽

Sang-Hoon Kim ◽

...

Keyword(s):

Growth Factor ◽

Combination Therapy ◽

Distress Syndrome ◽

Collagen Type ◽

Human Lung ◽

A549 Cells ◽

Collagen Type I ◽

Type I ◽

Tnf Α ◽

Lung Epithelial

Purpose: Acute respiratory distress syndrome (ARDS) is characterized by its acute onset of symptoms such as bilateral pulmonary infiltrates, severe hypoxemia, and pulmonary edema. Many patients with ARDS survive in the acute phase, but then die from significant lung fibrosis.Methods: The effect of combination therapy with polydeoxyribonucleotide (PDRN) and pirfenidone on ARDS was investigated using human lung epithelial A549 cells. ARDS environment was induced by treatment with lipopolysaccharide and transforming growth factor (TGF)-β. Enzyme-linked immunoassay for connective tissue growth factor (CTGF) and hydroxyproline were conducted. Western blot for collagen type I, fibroblast growth factor (FGF), tumor necrosis factor (TNF)-α, and interleukin (IL)-6 was performed.Results: In this study, 8-μg/mL PDRN enhanced cell viability. Combination therapy with PDRN and pirfenidone and pirfenidone monotherapy suppressed expressions of CTGF and hydroxyproline and inhibited expressions of collagen type I and FGF. Combination therapy with PDRN and pirfenidone and PDRN monotherapy suppressed expression of TNF-α and IL-1β.Conclusions: The combination therapy with PDRN and pirfenidone exerted stronger therapeutic effect against lipopolysaccharide and TGF-β-induced ARDS environment compared to the PDRN monotherapy or pirfenidone monotherapy. The excellent therapeutic effect of combination therapy with PDRN and pirfenidone on ARDS was shown by promoting the rapid anti-inflammatory effect and inhibiting the fibrotic processes.

Download Full-text