scholarly journals E3 ligase TRIM47 positively regulates endothelial activation and pulmonary inflammation through potentiating the K63-linked ubiquitination

2021 ◽  
Author(s):  
Yisong Qian ◽  
Ziwei Wang ◽  
Hongru Lin ◽  
Tianhua Lei ◽  
Zhou Zhou ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Inflammatory Response ◽  
Signaling Pathways ◽  
Pulmonary Inflammation ◽  
Endothelial Activation ◽  
Mapk Signaling ◽  
Monocyte Adhesion ◽  
Mapk Signaling Pathways

Endothelial activation plays an essential role in the pathology of sepsis-induced acute lung injury, but the detailed regulatory mechanisms remain largely unknown. Here, we demonstrated that TRIM47, an ubiquitin E3 ligase of tripartite protein family, is highly expressed in vascular endothelial cells and is up-regulated during TNFα-induced endothelial activation. Knockdown of TRIM47 in endothelial cells prevents the transcription of multiple pro-inflammatory cytokines, reduces monocyte adhesion and the expression of adhesion molecules, and inhibits the secretion of IL-1β and IL-6 into the supernatant. By contrast, overexpression of TRIM47 promotes inflammatory response and monocyte adhesion upon TNFα stimulation. TRIM47 modulates the activation of NF-κB and MAPK signaling pathways during endothelial activation. Further experiment confirmed that TRIM47 interacts with TRAF2 and mediates K63-linked ubiquitination. In addition, TRIM47-deficient mice are more resistant to lipopolysaccharide-induced acute lung injury and death, due to attenuated pulmonary inflammation. Taken together, our studies suggest that TRIM47 promotes pulmonary inflammation and injury at least partly through potentiating the K63-linked ubiquitination of TRAF2, which in turn activates NF-κB and MAPK signaling pathways to trigger inflammatory response in endothelial cells.

Inducing inflammatory response in RAW264.7 and NK-92 cells by an arabinogalactan isolated from Ferula gummosa via NF-κB and MAPK signaling pathways

2020 ◽  
Vol 241 ◽  
pp. 116358
Author(s):  
Mehdi Tabarsa ◽  
Elham Hashem Dabaghian ◽  
SangGuan You ◽  
Khamphone Yelithao ◽  
Subramanian Palanisamy ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Signaling Pathways ◽  
Mapk Signaling ◽  
Mapk Signaling Pathways

scholarly journals Association of Toll-Like Receptor Signaling and Reactive Oxygen Species: A Potential Therapeutic Target for Posttrauma Acute Lung Injury

2010 ◽  
Vol 2010 ◽  
pp. 1-8 ◽  
Author(s):  
Meng Xiang ◽  
Janet Fan ◽  
Jie Fan
Keyword(s):  
Reactive Oxygen Species ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Inflammatory Response ◽  
Therapeutic Target ◽  
Major Trauma ◽  
Pulmonary Inflammation ◽  
Reactive Oxygen ◽  
Oxygen Species

Acute lung injury (ALI) frequently occurs in traumatic patients and serves as an important component of systemic inflammatory response syndrome (SIRS). Hemorrhagic shock (HS) that results from major trauma promotes the development of SIRS and ALI by priming the innate immune system for an exaggerated inflammatory response. Recent studies have reported that the mechanism underlying the priming of pulmonary inflammation involves the complicated cross-talk between Toll-like receptors (TLRs) and interactions between neutrophils (PMNs) and alveolar macrophages (AMϕ) as well as endothelial cells (ECs), in which reactive oxygen species (ROS) are the key mediator. This paper summarizes some novel mechanisms underlying HS-primed lung inflammation focusing on the role of TLRs and ROS, and therefore suggests a new therapeutic target for posttrauma ALI.

Expression of p38 MAPK in Acute Lung Injury Induced by LPS in Mice

2014 ◽  
Vol 522-524 ◽  
pp. 332-336 ◽  
Author(s):  
Kai Xiu Qin ◽  
Yong Wang ◽  
Hua Gang Jian
Keyword(s):  
Endothelial Cells ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
P38 Mapk ◽  
Inflammatory Cells ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Control Group ◽  
Mitogen Activated Protein ◽  
Set Up

Objective To investigate the expression and roles of p38 mitogen-activated protein kinase (p38 MAPK) in LPS-induced acute lung injury (ALI) in mice. Methods The ALI mice models were set up by intraperineal injection of lipopolysaccharide (LPS). The expressions of p38 MAPK in lung tissues were detected by immunohistochemistry and Western-blot. Results The positive expressions of p38 MAPK distribute mainly in infiltrative inflammatory cells, epithelial cells and endothelial cells. And the level of expression of phosphated p38 MAPK in ALI group were higher obviously than that in the control group, and it reached a peak after two hours. Conclusion p38 MAPK signaling pathway was triggered by ALI induced by endotoxin.

scholarly journals The Disruption of the Endothelial Barrier Contributes to Acute Lung Injury Induced by Coxsackievirus A2 Infection in Mice

2021 ◽  
Vol 22 (18) ◽  
pp. 9895
Author(s):  
Wangquan Ji ◽  
Qiang Hu ◽  
Mengdi Zhang ◽  
Chuwen Zhang ◽  
Chen Chen ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Pulmonary Edema ◽  
Foot And Mouth Disease ◽  
Epidemiological Studies ◽  
Mapk Signaling ◽  
Lung Damage ◽  
Mitogen Activated Protein Kinase ◽  
Endothelial Barrier

Sporadic occurrences and outbreaks of hand, foot, and mouth disease (HFMD) caused by Coxsackievirus A2 (CVA2) have frequently reported worldwide recently, which pose a great challenge to public health. Epidemiological studies have suggested that the main cause of death in critical patients is pulmonary edema. However, the pathogenesis of this underlying comorbidity remains unclear. In this study, we utilized the 5-day-old BALB/c mouse model of lethal CVA2 infection to evaluate lung damage. We found that the permeability of lung microvascular was significantly increased after CVA2 infection. We also observed the direct infection and apoptosis of lung endothelial cells as well as the destruction of tight junctions between endothelial cells. CVA2 infection led to the degradation of tight junction proteins (e.g., ZO-1, claudin-5, and occludin). The gene transcription levels of von Willebrand factor (vWF), endothelin (ET), thrombomodulin (THBD), granular membrane protein 140 (GMP140), and intercellular cell adhesion molecule-1 (ICAM-1) related to endothelial dysfunction were all significantly increased. Additionally, CVA2 infection induced the increased expression of inflammatory cytokines (IL-6, IL-1β, and MCP-1) and the activation of p38 mitogen-activated protein kinase (MAPK). In conclusion, the disruption of the endothelial barrier contributes to acute lung injury induced by CVA2 infection; targeting p38-MAPK signaling may provide a therapeutic approach for pulmonary edema in critical infections of HFMD.

scholarly journals Down-regulation of miR-let-7e attenuates LPS-induced acute lung injury in mice via inhibiting pulmonary inflammation by targeting SCOS1/NF-κB pathway

2021 ◽  
Vol 41 (1) ◽  
Author(s):  
Wuquan Li ◽  
Wentao Zhang ◽  
Jun Liu ◽  
Yalong Han ◽  
He Jiang ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Inflammatory Response ◽  
Inflammatory Diseases ◽  
Pulmonary Inflammation ◽  
Lavage Fluid ◽  
Luciferase Reporter ◽  
Cytokine Signaling ◽  
Down Regulation ◽  
Reporter Assays

Abstract Excessive pulmonary inflammatory response is critical in the development of acute lung injury (ALI). Previously, microRNAs (miRNAs) have been recognized as an important regulator of inflammation in various diseases. However, the effects and mechanisms of miRNAs on inflammatory response in ALI remain unclear. Herein, we tried to screen miRNAs in the processes of ALI and elucidate the potential mechanism. Using a microarray assay, microRNA let-7e (let-7e) was chose as our target for its reported suppressive roles in several inflammatory diseases. Down-regulation of let-7e by antagomiR-let-7e injection attenuated LPS-induced acute lung injury. We also found that antagomiR-let-7e could obviously improve the survival rate in ALI mice. Moreover, antagomiR-let-7e treatment reduced the production of proinflammatory cytokines (i.e., TNF-α, IL-1β and IL-6) in bronchoalveolar lavage fluid (BALF) of LPS-induced ALI mice. Luciferase reporter assays confirmed that suppressor of cytokine signaling 1 (SOCS1), a powerful attenuator of nuclear factor kappa B (NF-κB) signaling pathway, was directly targeted and suppressed by let-7e in RAW264.7 cells. In addition, it was further observed that SOCS1 was down-regulated, and inversely correlated with let-7e expression levels in lung tissues of ALI mice. Finally, down-regulation of let-7e suppressed the activation of NF-κB pathway, as evidenced by the reduction of p-IκBα, and nuclear p-p65 expressions in ALI mice. Collectively, our findings indicate that let-7e antagomir protects mice against LPS-induced lung injury via repressing the pulmonary inflammation though regulation of SOCS1/NF-κB pathway, and let-7e may act as a potential therapeutic target for ALI.

HB-EGF promotes angiogenesis in endothelial cells via PI3-kinase and MAPK signaling pathways

2007 ◽  
Vol 25 (4) ◽  
pp. 253-263 ◽  
Author(s):  
Veela B. Mehta ◽  
Gail E. Besner ◽  
Veela B. Mehta ◽  
Gail E. Besner
Keyword(s):  
Endothelial Cells ◽  
Signaling Pathways ◽  
Mapk Signaling ◽  
Pi3 Kinase ◽  
Mapk Signaling Pathways
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