Cardamonin inhibits LPS-induced inflammatory responses and prevents acute lung injury by targeting myeloid differentiation factor 2

We have examined the mechanism underlying amelioration of sepsis-induced acute lung injury by chelidonine in newborn mice. To this end, a sepsis model was established using cecal ligation and puncture in newborn mice. The sepsis-induced acute lung injury was associated with an increased inflammatory infiltration and pulmonary congestion, as well as abnormal alveolar morphology. The lung injury-associated increased tumor necrosis factor-α and interleukin-1β in bronchoalveolar lavage fluid and lung, the markers of inflammatory infiltration and pulmonary congestion, diminished by chelidonine treatment. Chelidonine administration also downregulated protein levels of toll-like receptor 4, myeloid differentiation factor 88, phosphorylated nuclear factor-kappa B, and nuclear factor-kappa B that are elevated in response to sepsis. In conclusion, chelidonine provides a potential therapeutic strategy for newborn mice with acute lung injury.

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Bilobalide Ameliorates Sepsis Induced Acute Lung Injury by Inactivating Toll-Like Receptor 4/Myeloid Differentiation Factor 88/Nuclear Factor-Kappa B Pathway

Current Topics in Nutraceutical Research ◽

10.37290/ctnr2641-452x.19:277-282 ◽

2020 ◽

Vol 19 (3) ◽

pp. 277-282

Author(s):

Tian Liu ◽

Siyi Jiang ◽

Shengwei Jia ◽

Fuxiang Fan

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Nuclear Factor Kappa B ◽

Cecal Ligation ◽

Myeloid Differentiation ◽

Nuclear Factor ◽

Cecal Ligation And Puncture ◽

Toll Like Receptor ◽

Toll Like Receptor 4 ◽

Myeloid Differentiation Factor

Acute lung injury refers to the injury of alveolar epithelial cells and pulmonary capillary endothelial cells caused by noncardiac factors. To better combat the disease, there is an urgent need to develop more effective drugs. Sepsis is a syndrome of systemic inflammation caused by infection, and the molecular mechanism by which sepsis induces acute lung injury has not been clearly determined. Bilobalide is a unique component of Ginkgo biloba. Although it has multiple biological functions, its role in sepsis induced acute lung injury needs further study. In this study, we found that bilobalide alleviated cecal ligation and puncture induced acute lung injury. Additionally, bilobalide regulated cecal ligation and puncture induced lung injury through toll-like receptor 4/myeloid differentiation factor 88/nuclear factor-kappa B pathway. We therefore conclude that bilobalide may be a potential drug for the treatment of sepsis induced acute lung injury.

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Arachidonic acid inhibits inflammatory responses by binding to myeloid differentiation factor-2 (MD2) and preventing MD2/toll-like receptor 4 signaling activation

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease ◽

10.1016/j.bbadis.2020.165683 ◽

2020 ◽

Vol 1866 (5) ◽

pp. 165683 ◽

Cited By ~ 5

Author(s):

Yali Zhang ◽

Hongjin Chen ◽

Wenxin Zhang ◽

Yan Cai ◽

Peiren Shan ◽

...

Keyword(s):

Arachidonic Acid ◽

Inflammatory Responses ◽

Myeloid Differentiation ◽

Toll Like Receptor ◽

Toll Like Receptor 4 ◽

Differentiation Factor ◽

Signaling Activation ◽

Myeloid Differentiation Factor

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Toll-like Receptor 4-Myeloid Differentiation Factor 88 Signaling Contributes to Ventilator-induced Lung Injury in Mice

Anesthesiology ◽

10.1097/aln.0b013e3181e89ab2 ◽

2010 ◽

Vol 113 (3) ◽

pp. 619-629 ◽

Cited By ~ 15

Author(s):

Huihua Li ◽

Xiaoli Su ◽

Xuebin Yan ◽

Karla Wasserloos ◽

Wei Chao ◽

...

Keyword(s):

Lung Injury ◽

Myeloid Differentiation ◽

Toll Like Receptor ◽

Wild Type ◽

Toll Like Receptor 4 ◽

Ventilator Induced Lung Injury ◽

Differentiation Factor ◽

Extracellular Signal ◽

Myd88 Signaling ◽

Myeloid Differentiation Factor

Background The mechanisms of ventilator-induced lung injury, an iatrogenic inflammatory condition induced by mechanical ventilation, are not completely understood. Toll-like receptor 4 (TLR4) signaling via the adaptor protein myeloid differentiation factor 88 (MyD88) is proinflammatory and plays a critical role in host immune response to invading pathogen and noninfectious tissue injury. The role of TLR4-MyD88 signaling in ventilator-induced lung injury remains incompletely understood. Methods Mice were ventilated with low or high tidal volume (HTV), 7 or 20 ml/kg, after tracheotomy for 4 h. Control mice were tracheotomized without ventilation. Lung injury was assessed by: alveolar capillary permeability to Evans blue albumin, wet/dry ratio, bronchoalveolar lavage analysis for cell counts, total proteins and cytokines, results of histopathological examination of the lung, and plasma cytokine levels. Results Wild-type mice subjected to HTV had increased pulmonary permeability, inflammatory cell infiltration/lung edema, and interleukin-6/macrophage-inflammatory protein-2 in the lavage compared with control mice. In HTV, levels of inhibitor of kappaB alpha decreased, whereas phosphorylated extracellular signal-regulated kinases increased. TLR4 mutant and MyD88 mice showed markedly attenuated response to HTV, including less lung inflammation, pulmonary edema, cell number, protein content, and the cytokines in the lavage. Furthermore, compared with wild-type mice, both TLR4 mutant and MyD88 mice had significantly higher levels of inhibitor of kappaB alpha and reduced extracellular signal-regulated kinase phosphorylation after HTV. Conclusions TLR4-MyD88 signaling plays an important role in the development of ventilator-induced lung injury in mice, possibly through mechanisms involving nuclear factor-kappaB and mitogen-activated protein kinase pathways.

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Cutting Edge: Protective Cell-Mediated Immunity to Listeria monocytogenes in the Absence of Myeloid Differentiation Factor 88

The Journal of Immunology ◽

10.4049/jimmunol.171.2.533 ◽

2003 ◽

Vol 171 (2) ◽

pp. 533-537 ◽

Cited By ~ 62

Author(s):

Sing Sing Way ◽

Tobias R. Kollmann ◽

Adeline M. Hajjar ◽

Christopher B. Wilson

Keyword(s):

Listeria Monocytogenes ◽

Cutting Edge ◽

Myeloid Differentiation ◽

Cell Mediated Immunity ◽

Differentiation Factor ◽

Myeloid Differentiation Factor 88 ◽

Myeloid Differentiation Factor

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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.

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