Luteolin Suppresses Inflammatory Mediator Expression by Blocking the Akt/NFκB Pathway in Acute Lung Injury Induced by Lipopolysaccharide in Mice

Acute lung injury (ALI), instilled by lipopolysaccharide (LPS), is a severe illness with excessive mortality and has no specific treatment strategy. Luteolin is an anti-inflammatory flavonoid and widely distributed in the plants. Pretreatment with luteolin inhibited LPS-induced histological changes of ALI and lung tissue edema. In addition, LPS-induced inflammatory responses, including increased vascular permeability, tumor necrosis factor (TNF)-αand interleukin (IL)-6 production, and expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), were also reduced by luteolin in a concentration-dependent manner. Furthermore, luteolin suppressed activation of NFκB and its upstream molecular factor, Akt. These results suggest that the protection mechanism of luteolin is by inhibition of NFκB activation possibly via Akt.

Download Full-text

Inhibition of cytochrome P-450 attenuates hypoxemia of acute lung injury in dogs

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1996.270.4.h1355 ◽

1996 ◽

Vol 270 (4) ◽

pp. H1355-H1362 ◽

Cited By ~ 6

Author(s):

A. H. Stephenson ◽

R. S. Sprague ◽

N. L. Weintraub ◽

L. McMurdo ◽

A. J. Lonigro

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Dependent Manner ◽

Venous Admixture ◽

Epoxyeicosatrienoic Acid ◽

Lung Water ◽

Concentration Dependent Manner ◽

Prostaglandin F2 Alpha ◽

Pulmonary Vasodilator ◽

Cytochrome P 450

The intravenous administration of ethchlorvynol (ECV), in dogs, resulted in an acute lung injury (ALI) characterized by a 200 +/- 80% increase in venous admixture and a 142 +/- 30% increase in extravascular lung water (EVLW). Pretreatment with the cytochrome P-450 inhibitor 8-methoxypsoralen prevented the ECV-induced increase in venous admixture but not the increased EVLW. These findings parallel those reported for cyclooxygenase inhibition in ECV-induced ALI and suggest that an arachidonic acid (AA) metabolite of pulmonary cytochrome P-450 activity may mediate the increase in venous admixture of ALI. We demonstrate that canine pulmonary microsomes metabolize [1-(14)C]AA to a variety of products, including the cytochrome P-450 metabolites 5,6-, 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid (EET). In prostaglandin F2 alpha-contracted, isolated pulmonary venous rings, 5,6-EET induced relaxation in a concentration-dependent manner. This action of 5,6-EET was prevented by indomethacin (10(-5) M). These results suggest that may serve as the cyclooxygenase-dependent endogenous pulmonary vasodilator responsible for the increase in venous admixture of ECV-induced ALI.

Download Full-text

Essential Role of Visfatin in Lipopolysaccharide and Colon Ascendens Stent Peritonitis-Induced Acute Lung Injury

International Journal of Molecular Sciences ◽

10.3390/ijms20071678 ◽

2019 ◽

Vol 20 (7) ◽

pp. 1678 ◽

Cited By ~ 1

Author(s):

Yi-Chen Lee ◽

Chun-Yu Lin ◽

Yen-Hsu Chen ◽

Wen-Chin Chiu ◽

Yen-Yun Wang ◽

...

Keyword(s):

Acute Lung Injury ◽

Epithelial Cell ◽

Lung Injury ◽

Cell Lines ◽

Inflammatory Cytokines ◽

Bronchial Epithelial Cell ◽

Bronchial Epithelial ◽

Epithelial Cell Lines ◽

Nfκb Pathway ◽

Pro Inflammatory Cytokines

Acute lung injury (ALI) is a life-threatening syndrome characterized by acute and severe hypoxemic respiratory failure. Visfatin, which is known as an obesity-related cytokine with pro-inflammatory activities, plays a role in regulation of inflammatory cytokines. The mechanisms of ALI remain unclear in critically ill patients. Survival in ALI patients appear to be influenced by the stress generated by mechanical ventilation and by ALI-associated factors that initiate the inflammatory response. The objective for this study was to understand the mechanisms of how visfatin regulates inflammatory cytokines and promotes ALI. The expression of visfatin was evaluated in ALI patients and mouse sepsis models. Moreover, the underlying mechanisms were investigated using human bronchial epithelial cell lines, BEAS-2B and NL-20. An increase of serum visfatin was discovered in ALI patients compared to normal controls. Results from hematoxylin and eosin (H&E) and immunohistochemistry staining also showed that visfatin protein was upregulated in mouse sepsis models. Moreover, lipopolysaccharide (LPS) induced visfatin expression, activated the STAT3/NFκB pathway, and increased the expression of pro-inflammatory cytokines, including IL1-β, IL-6, and TNF-α in human bronchial epithelial cell lines NL-20 and BEAS-2B. Co-treatment of visfatin inhibitor FK866 reversed the activation of the STAT3/NFκB pathway and the increase of pro-inflammatory cytokines induced by LPS. Our study provides new evidence for the involvement of visfatin and down-stream events in acute lung injury. Further studies are required to confirm whether the anti-visfatin approaches can improve ALI patient survival by alleviating the pro-inflammatory process.

Download Full-text

High concentration of hydrogen ameliorates lipopolysaccharide-induced acute lung injury in a sirt1-dependent manner

Respiratory Physiology & Neurobiology ◽

10.1016/j.resp.2021.103808 ◽

2021 ◽

pp. 103808

Author(s):

Junfeng Du ◽

Jingwen Li ◽

Rongqin Li ◽

Xixin Yan

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Dependent Manner ◽

High Concentration

Download Full-text

LncRNA HOTAIR Increases Inflammatory Responses by Activating NF-κB Pathway in LPS-Induced Acute Lung Injury

10.21203/rs.3.rs-49969/v1 ◽

2020 ◽

Author(s):

XiaoMei Huang ◽

ZeXun Mo ◽

YuJun Li ◽

Hua He ◽

KangWei Wang ◽

...

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Noncoding Rna ◽

Nuclear Translocation ◽

Inflammatory Responses ◽

A549 Cells ◽

Enzyme Linked Immunosorbent Assay ◽

Qrt Pcr ◽

Tnf Α ◽

Lncrna Hotair

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.

Download Full-text

Protective effect of Cordyceps sinensis extract on lipopolysaccharide-induced acute lung injury in mice

Bioscience Reports ◽

10.1042/bsr20190789 ◽

2019 ◽

Vol 39 (6) ◽

Cited By ~ 6

Author(s):

Shuiqiao Fu ◽

Weina Lu ◽

Wenqiao Yu ◽

Jun Hu

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Protective Effect ◽

Weight Ratio ◽

Cordyceps Sinensis ◽

Myeloperoxidase Activity ◽

Mrna Levels ◽

Dependent Manner ◽

Tnf Α ◽

Cox 2

Abstract Background: To study the protective effect of Cordyceps sinensis extract (Dong Chong Xia Cao in Chinese [DCXC]) on experimental acute lung injury (ALI) mice. Methods and results: ALI model was induced by intratracheal-instilled lipopolysaccharide (LPS, 2.4 mg/kg) in BALB/c male mice. The mice were administrated DCXC (ig, 10, 30, 60 mg/kg) in 4 and 8 h after receiving LPS. Histopathological section, wet/dry lung weight ratio and myeloperoxidase activity were detected. Bronchoalveolar lavage fluid (BALF) was collected for cell count, the levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6) and nitric oxide (NO) in BALF was detected by ELISA, the protein and mRNA expression of nuclear factor-κB p65 (NF-κB p65), inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) in lung tissue was detected by Western blot and RT-PCR. The result showed that DCXC could reduce the degree of histopathological injury, wet/dry weight ratio (W/D ratio) and myeloperoxidase activity (P<0.05) with a dose-dependent manner. The increased number of total cells, neutrophils and macrophages in BALF were significantly inhibited by DCXC treatment (P<0.05). The increased levels of TNF-α, IL-1β, IL-6 and NO in BALF after LPS administration was significantly reduced by DCXC (P<0.05). In addition, the increased protein and mRNA levels of iNOS, COX-2 and NF-κB p65 DNA binding ability in LPS group were dose-dependently reduced by DCXC treatment (P<0.05). Conclusion: DCXC could play an anti-inflammatory and antioxidant effect on LPS-induced ALI through inhibiting NF-κB p65 phosphorylation, and the expression of COX-2 and iNOS in lung. The result showed that DCXC has a potential protective effect on the ALI.

Download Full-text

Natural Antioxidant Betanin Protects Rats from Paraquat-Induced Acute Lung Injury Interstitial Pneumonia

BioMed Research International ◽

10.1155/2015/608174 ◽

2015 ◽

Vol 2015 ◽

pp. 1-9 ◽

Cited By ~ 15

Author(s):

Junyan Han ◽

Deshun Ma ◽

Miao Zhang ◽

Xuelian Yang ◽

Dehong Tan

Keyword(s):

Body Weight ◽

Acute Lung Injury ◽

Lung Injury ◽

Weight Ratio ◽

Lavage Fluid ◽

Dependent Manner ◽

Sod Activity ◽

Protein Levels ◽

Injury Characteristic ◽

Dose Dependent

The effect of betanin on a rat paraquat-induced acute lung injury (ALI) model was investigated. Paraquat was injected intraperitoneally at a single dose of 20 mg/kg body weight, and betanin (25 and 100 mg/kg/d) was orally administered 3 days before and 2 days after paraquat administration. Rats were sacrificed 24 hours after the last betanin dosage, and lung tissue and bronchoalveolar lavage fluid (BALF) were collected. In rats treated only with paraquat, extensive lung injury characteristic of ALI was observed, including histological changes, elevation of lung : body weight ratio, increased lung permeability, increased lung neutrophilia infiltration, increased malondialdehyde (MDA) and myeloperoxidase (MPO) activity, reduced superoxide dismutase (SOD) activity, reduced claudin-4 and zonula occluden-1 protein levels, increased BALF interleukin (IL-1) and tumor necrosis factor (TNF)-αlevels, reduced BALF IL-10 levels, and increased lung nuclear factor kappa (NF-κB) activity. In rats treated with betanin, paraquat-induced ALI was attenuated in a dose-dependent manner. In conclusion, our results indicate that betanin attenuates paraquat-induced ALI possibly via antioxidant and anti-inflammatory mechanisms. Thus, the potential for using betanin as an auxilliary therapy for ALI should be explored further.

Download Full-text

NEMO-Binding Domain Peptide Attenuates Lipopolysaccharide-Induced Acute Lung Injury by Inhibiting the NF-κB Signaling Pathway

Mediators of Inflammation ◽

10.1155/2016/7349603 ◽

2016 ◽

Vol 2016 ◽

pp. 1-11 ◽

Cited By ~ 6

Author(s):

Jianhua Huang ◽

Li Li ◽

Weifeng Yuan ◽

Linxin Zheng ◽

Zhenhui Guo ◽

...

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Signaling Pathway ◽

Binding Domain ◽

Dependent Manner ◽

Protective Effects ◽

Lps Challenge ◽

Domain Peptide ◽

Nemo Binding Domain ◽

Dose Dependent

The aim of the present study is to investigate the protective effects and relevant mechanisms exerted by NEMO-binding domain peptide (NBD) against lipopolysaccharide- (LPS-) induced acute lung injury (ALI) in mice. The ALI model was induced by intratracheally administered atomized LPS (5 mg/kg) to BABL/c mice. Half an hour before LPS administration, we treated the mice with increasing concentrations of intratracheally administered NBD or saline aerosol. Two hours after LPS administration, each group of mice was sacrificed. We observed that NBD pretreatment significantly attenuated LPS-induced lung histopathological injury in a dose-dependent manner. Western blotting established that NBD pretreatment obviously attenuated LPS-induced IκB-αand NF-κBp65 activation and NOX1, NOX2, and NOX4 overexpression. Furthermore, NBD pretreatment increased SOD and T-AOC activity and decreased MDA levels in lung tissue. In addition, NBD also inhibited TNF-αand IL-1βsecretion in BALF after LPS challenge. In conclusion, NBD protects against LPS-induced ALI in mice.

Download Full-text

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.

Download Full-text

Modulatory effect of antibiotics on cytokine production by human monocytes in vitro.

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.40.6.1366 ◽

1996 ◽

Vol 40 (6) ◽

pp. 1366-1370 ◽

Cited By ~ 132

Author(s):

K Morikawa ◽

H Watabe ◽

M Araake ◽

S Morikawa

Keyword(s):

Antimicrobial Agents ◽

Inflammatory Responses ◽

Interleukin 1 ◽

Immunomodulatory Activity ◽

Lymphocyte Function ◽

Dependent Manner ◽

Human Monocytes ◽

Concentration Dependent Manner ◽

Cytokine Synthesis

Some antimicrobial agents have been reported to modify the host immune and inflammatory responses both in vivo and in vitro. Fosfomycin (FOM) and clarithromycin (CAM) have immunomodulatory activity on human lymphocyte function. In the present study, we examined the effects of FOM and CAM on cytokine synthesis by lipopolysaccharide (LPS)-stimulated human monocytes in comparison with that of dexamethasone in vitro. The three drugs demonstrated positive or negative effects on the synthesis of various cytokines by LPS-primed monocytes. They suppressed the synthesis of tumor necrosis factor alpha, interleukin 1 alpha (IL-1 alpha), IL-1 beta, the IL-1 receptor antagonist, and granulocyte-macrophage colony-stimulating factor in a concentration-dependent manner at concentrations between 1.6 and 40 micrograms/ml. On the contrary, the drugs showed different actions on the synthesis of IL-6 and IL-10. Namely, FOM enhanced both IL-6 and IL-10 synthesis, CAM enhanced only IL-10 synthesis, but dexamethasone deeply suppressed the synthesis of both cytokines. These data indicate that antibacterial agents may modify acute-phase inflammatory responses through their effects on cytokine synthesis by monocytes.

Download Full-text