Umbelliferone Alleviates Lipopolysaccharide-Induced Inflammatory Responses in Acute Lung Injury by Down-Regulating TLR4/MyD88/NF-κB Signaling

Abstract Background Nuclear factor kappa-B (NF-κB) activation increased the expression of cytokines and further lead to lung injury was considered the main mechanism of acute lung injury (ALI). Here, we focus on exploring the potential regulatory mechanism between long noncoding RNA (LncRNA) HOX transcript antisense RNA (HOTAIR) and NF-κB on LPS-induced ALI. Methods A549 cells were then divided into 4 groups: HOTAIR group, NC group, si-HOTAIR group and si-NC group. These 4 groups were then treated with 1μg/mL lipopolysaccharides (LPS) or without LPS at 37°C for 24 h. The expression level of cytokines (tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6) and LncRNA HOTAIR were evaluated by quantitative Real Time Polymerase Chain Reaction (qRT-PCR) and Enzyme-linked immunosorbent assay (ELISA). Western Blot analysis was adopted for evaluating the level of p-IκBα/IκBα and p-p65/p65. Nuclear translocation of p65 was observed by immunofluorescence staining. Results qRT-PCR and ELISA assay showed that the expression of cytokines (IL-1β, IL-6 and TNF-α) and inflammatory gene HOTAIR was remarkably increased with LPS treatment (p < 0.01). Over-expression of HOTAIR significantly increased the expression of cytokines (including IL-1β, IL-6 and TNF-α) and NF-κB pathway associated proteins (including p-IκBα/IκBα and p-p65/p65), while knockdown of HOTAIR had the opposite effect (p < 0.01). The immunofluorescence assay showed that the level of p65 in the nucleus was significantly higher in the HOTAIR group and significantly lowers in the si-HOTAIR group (p < 0.01). Conclusion HOTAIR may play a pro-inflammatory response through NF-κB pathway in LPS-induced ALI, which may provide a perspective for further understanding the pathogenic mechanism of ALI.

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Levonadifloxacin, a Novel Benzoquinolizine Fluoroquinolone, Modulates Lipopolysaccharide-Induced Inflammatory Responses in Human Whole-Blood Assay and Murine Acute Lung Injury Model

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00084-20 ◽

2020 ◽

Vol 64 (5) ◽

Author(s):

Anasuya Patel ◽

Ganesh V. Sangle ◽

Jinal Trivedi ◽

Sushant A. Shengule ◽

Deepak Thorve ◽

...

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Whole Blood ◽

Inflammatory Responses ◽

Immunomodulatory Activity ◽

Human Whole Blood ◽

Injury Model ◽

Cytokine Levels ◽

Lung Injury Model ◽

Clinical Benefits

ABSTRACT Fluoroquinolones are reported to possess immunomodulatory activity; hence, a novel benzoquinolizine fluoroquinolone, levonadifloxacin, was evaluated in lipopolysaccharide-stimulated human whole-blood (HWB) and mouse acute lung injury (ALI) models. Levonadifloxacin significantly mitigated the inflammatory responses in an HWB assay through inhibition of proinflammatory cytokines and in the ALI model by lowering lung total white blood cell count, myeloperoxidase, and cytokine levels. The immunomodulatory effect of levonadifloxacin, along with promising antibacterial activity, is expected to provide clinical benefits in the treatment of infections.

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Src protein tyrosine kinase family and acute inflammatory responses

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00261.2005 ◽

2006 ◽

Vol 291 (2) ◽

pp. L129-L141 ◽

Cited By ~ 111

Author(s):

Daisuke Okutani ◽

Monika Lodyga ◽

Bing Han ◽

Mingyao Liu

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Tyrosine Kinase ◽

Reperfusion Injury ◽

Protein Tyrosine Kinase ◽

Inflammatory Responses ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Critical Role ◽

Protein Tyrosine

Acute inflammatory responses are one of the major underlying mechanisms for tissue damage of multiple diseases, such as ischemia-reperfusion injury, sepsis, and acute lung injury. By use of cellular and molecular approaches and transgenic animals, Src protein tyrosine kinase (PTK) family members have been identified to be essential for the recruitment and activation of monocytes, macrophages, neutrophils, and other immune cells. Src PTKs also play a critical role in the regulation of vascular permeability and inflammatory responses in tissue cells. Importantly, animal studies have demonstrated that small chemical inhibitors for Src PTKs attenuate tissue injury and improve survival from a variety of pathological conditions related to acute inflammatory responses. Further investigation may lead to the clinical application of these inhibitors as drugs for ischemia-reperfusion injury (such as stroke and myocardial infarction), sepsis, acute lung injury, and multiple organ dysfunction syndrome.

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Effect of MiR-16 on Acute Lung Injury in Neonatal Rats Through Regulating NF-κB Pathway

Journal of Biomaterials and Tissue Engineering ◽

10.1166/jbt.2020.2263 ◽

2020 ◽

Vol 10 (3) ◽

pp. 360-364

Author(s):

Yan Xing ◽

Yuan Liang ◽

Changsong Shi ◽

Yudong Miao ◽

Jianqin Gu ◽

...

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Correlation Analysis ◽

Western Blotting ◽

Inflammatory Responses ◽

Morphological Changes ◽

Pearson Correlation ◽

Mrna Levels ◽

Low Oxygen ◽

Pearson Correlation Analysis

Acute lung injury represents a widespread, variable type of lung injury characterized by a low oxygen level in the blood, non cardiogenic pulmonary edema, low lung compliance and extensive capillary leakage. In our study, the Wistar rat mode of ALI was established using lipopolysaccharide (LPS). The rats were randomly divided into normal control (NC) group (n = 12) and miR-16 overex-pression group (n = 12), and they were transfected with empty vector and miR-16 overexpression virus, respectively. The lung tissues were extracted in both groups, and then the expression levels of miR-16 and NF-κB were detected via fluorescence quantitative reverse transcription-polymerase chain reaction (qRT-PCR), and the association between their expressions was analyzed via Pearson correlation analysis. Moreover, the morphological changes in lung tissues were detected via hematoxylin-eosin (HE) staining, and the differences in the wet/dry weight (W/D) ratio and the pathomorphological score of lung tissues were compared between the two groups. The expression level of NF-κB was detected via immunohistochemistry (IHC) and Western blotting. Our results showed that, there were different degrees of lung injury in lung tissues in both groups. In miR-16 overexpression group, the W/D ratio was significantly higher than that in NC group (P < 0.05), and the pathomorphological score was also significantly higher than that in NC group (P < 0.05). The results of RT-PCR revealed that the mRNA levels of miR-16 and NF-κB in miR-16 overexpression group were 2.5 and 3.7 times higher than those in NC group. The results of Western blotting and IHC also showed that the activity of NF-κB in lung tissues was evidently enhanced in miR-16 overexpression group compared with that in NC group. According to the Pearson correlation analysis, there was a significant positive correlation between the mRNA levels of miR-16 and NF-κB in lung tissues (r = 0.705, P = 0.012). In conclusion, miR-16 activates the NF-κB pathway to initiate a series of inflammatory responses, thereby contributing to the occurrence of ALI in rats.

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Propofol Potentiates Sevoflurane-Induced Inhibition of Nuclear Factor--κB-Mediated Inflammatory Responses and Regulation of Mitogen-Activated Protein Kinases Pathways via Toll-like Receptor 4 Signaling in Lipopolysaccharide-Induced Acute Lung Injury in Mice

The American Journal of the Medical Sciences ◽

10.1016/j.amjms.2017.06.012 ◽

2017 ◽

Vol 354 (5) ◽

pp. 493-505 ◽

Cited By ~ 8

Author(s):

Wei Liu ◽

Honghua Zhu ◽

Hao Fang

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Protein Kinases ◽

Inflammatory Responses ◽

Nuclear Factor Κb ◽

Nuclear Factor ◽

Toll Like Receptor ◽

Toll Like Receptor 4 ◽

Mitogen Activated Protein Kinases ◽

Mitogen Activated Protein

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Isorhamnetin protects mice from lipopolysaccharide-induced acute lung injury via the inhibition of inflammatory responses

Inflammation Research ◽

10.1007/s00011-015-0887-9 ◽

2015 ◽

Vol 65 (1) ◽

pp. 33-41 ◽

Cited By ~ 15

Author(s):

Gefu Chi ◽

Weiting Zhong ◽

Yan Liu ◽

Gejin Lu ◽

Hongming Lü ◽

...

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Inflammatory Responses

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The HMGB1-RAGE axis mediates traumatic brain injury–induced pulmonary dysfunction in lung transplantation

Science Translational Medicine ◽

10.1126/scitranslmed.3009443 ◽

2014 ◽

Vol 6 (252) ◽

pp. 252ra124-252ra124 ◽

Cited By ~ 59

Author(s):

Daniel J. Weber ◽

Adam S. A. Gracon ◽

Matthew S. Ripsch ◽

Amanda J. Fisher ◽

Bo M. Cheon ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Acute Lung Injury ◽

Brain Injury ◽

Lung Injury ◽

Lung Transplantation ◽

Inflammatory Responses ◽

Pulmonary Dysfunction ◽

Wild Type ◽

Hmgb1 Protein ◽

Lung Dysfunction

Traumatic brain injury (TBI) results in systemic inflammatory responses that affect the lung. This is especially critical in the setting of lung transplantation, where more than half of donor allografts are obtained postmortem from individuals with TBI. The mechanism by which TBI causes pulmonary dysfunction remains unclear but may involve the interaction of high-mobility group box-1 (HMGB1) protein with the receptor for advanced glycation end products (RAGE). To investigate the role of HMGB1 and RAGE in TBI-induced lung dysfunction, RAGE-sufficient (wild-type) or RAGE-deficient (RAGE−/−) C57BL/6 mice were subjected to TBI through controlled cortical impact and studied for cardiopulmonary injury. Compared to control animals, TBI induced systemic hypoxia, acute lung injury, pulmonary neutrophilia, and decreased compliance (a measure of the lungs’ ability to expand), all of which were attenuated in RAGE−/−mice. Neutralizing systemic HMGB1 induced by TBI reversed hypoxia and improved lung compliance. Compared to wild-type donors, lungs from RAGE−/−TBI donors did not develop acute lung injury after transplantation. In a study of clinical transplantation, elevated systemic HMGB1 in donors correlated with impaired systemic oxygenation of the donor lung before transplantation and predicted impaired oxygenation after transplantation. These data suggest that the HMGB1-RAGE axis plays a role in the mechanism by which TBI induces lung dysfunction and that targeting this pathway before transplant may improve recipient outcomes after lung transplantation.

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Adenovirus-delivered angiopoietin-1 suppresses NF-κB and p38 MAPK and attenuates inflammatory responses in phosgene-induced acute lung injury

Inhalation Toxicology ◽

10.3109/08958378.2013.872213 ◽

2014 ◽

Vol 26 (3) ◽

pp. 185-192 ◽

Cited By ~ 19

Author(s):

Dai-Kun He ◽

Yi-Ru Shao ◽

Lin Zhang ◽

Jie Shen ◽

Zhi-Yue Zhong ◽

...

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

P38 Mapk ◽

Inflammatory Responses ◽

Angiopoietin 1

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Biocompatible N-acetyl-nanoconstruct alleviates lipopolysaccharide-induced acute lung injury in vivo

Scientific Reports ◽

10.1038/s41598-021-01624-5 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Seongchan Kim ◽

Shin Young Kim ◽

Seung Joon Rho ◽

Seung Hoon Kim ◽

So Hyang Song ◽

...

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Inflammatory Responses ◽

Therapeutic Potential ◽

Intratracheal Instillation ◽

Sprague Dawley ◽

In Vivo Experiments ◽

Anti Inflammatory

AbstractOxidative stress plays important roles in inflammatory responses during acute lung injury (ALI). Recently, nanoconstruct (Nano)-based drug-delivery systems have shown promise in many models of inflammation. In this study, we evaluated the anti-inflammatory effects of N-acetylcysteine (NAC) loaded in a biocompatible Nano using a rat model of ALI. We synthesized a Nano with a good NAC-releasing capacity using porous silica Nano, which was used to produce Nano/NAC complexes. For in vivo experiments, Sprague–Dawley rats were intraperitoneally administered NAC or Nano/NAC 30 min after intratracheal instillation of lipopolysaccharide. After 6 h, bronchoalveolar lavage fluids and lung tissues were collected. The anti-oxidative effect of the Nano/NAC complex was confirmed by demonstrating reduced levels of reactive oxygen species after treatment with the Nano/NAC in vitro. In vivo experiments also showed that the Nano/NAC treatment may protect against LPS‐induced ALI thorough anti‐oxidative and anti‐inflammatory effects, which may be attributed to the inactivation of the NF‐κB and MAPK pathways. In addition, the effects of Nano/NAC treatment were shown to be superior to those of NAC alone. We suggest the therapeutic potential of Nano/NAC treatment as an anti‐inflammatory agent against ALI. Furthermore, our study can provide basic data for developing nanotechnology-based pharmacotherapeutics for ALI.

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