PECAM-1 protects against DIC by dampening inflammatory responses via inhibiting macrophage pyroptosis and restoring vascular barrier integrity

2020 ◽  
Vol 222 ◽  
pp. 1-16
Author(s):  
Lili Luo ◽  
Min Xu ◽  
Danying Liao ◽  
Jun Deng ◽  
Heng Mei ◽  
...  
2015 ◽  
Vol 63 (46) ◽  
pp. 10121-10130 ◽  
Author(s):  
Nguyen Quoc Tuan ◽  
Wonhwa Lee ◽  
Joonseok Oh ◽  
Roshan Rajan Kulkarni ◽  
Charlotte Gény ◽  
...  

2017 ◽  
Vol 595 (20) ◽  
pp. 6443-6462 ◽  
Author(s):  
Elzbieta Pluskota ◽  
Kamila M. Bledzka ◽  
Katarzyna Bialkowska ◽  
Dorota Szpak ◽  
Dmitry A. Soloviev ◽  
...  

2019 ◽  
Vol 12 (6) ◽  
pp. 1291-1303 ◽  
Author(s):  
Weimin Xu ◽  
Yuegui Guo ◽  
Zhenyu Huang ◽  
Haoxin Zhao ◽  
Mingxia Zhou ◽  
...  

2021 ◽  
Vol 8 ◽  
Author(s):  
Lili Qi ◽  
Haiguang Mao ◽  
Xiaohui Lu ◽  
Tingting Shi ◽  
Jinbo Wang

Cinnamaldehyde is an aromatic aldehyde isolated from the essential oil of cinnamon. It has been proved to possess various bioactivities such as anti-inflammation, anti-bacteria and antihypertensive. Nevertheless, early weaning could lead to intestinal stress, causing a range of intestinal health problems. The aim of this study is to explore the effects of cinnamaldehyde on gut barrier integrity, inflammatory responses, and intestinal microbiome of early weaned rats. In this study, treatment with cinnamaldehyde (100 or 200 mg/kg bodyweight/day) for 2 weeks significantly promoted the production of mucins in the colonic epithelial tissue of rats. Cinnamaldehyde supplementation significantly upregulated the expression of Muc2, TFF3 and the tight junction proteins (ZO-1, claudin-1, and occludin). Hematoxylin and eosin staining results showed that colonic histopathological changes were recovered by cinnamaldehyde supplementation. The mRNA expression of IL-6 and TNF-α were significantly decreased in the cinnamaldehyde groups while the TNF-α protein levels were significantly decreased in the two cinnamaldehyde groups. Cinnamaldehyde treatment obviously attenuated the activation of NF-κB signaling pathway in rat colonic tissue and suppressed the production of inflammatory cytokines. Furthermore, cinnamaldehyde supplementation remodeled the gut microbiome structure, at the genus level, Akkermansia, Bacteroides, Clostridium III, Psychrobacter, Intestinimonas were increased, whereas those of Ruminococcus, Escherichia/Shigella were obviously decreased in the cinnamaldehyde treated groups. These findings indicated that cinnamaldehyde could effectively enhance intestinal barrier integrity, ameliorate inflammatory responses and remodel gut microbiome in early weaned rats.


2015 ◽  
Vol 35 (suppl_1) ◽  
Author(s):  
Rohun U Palekar ◽  
Andrew P Jallouk ◽  
Hua Pan ◽  
Samuel A Wickline

Introduction: Thrombin plays a major role in regulating signaling pathways responsible for atherogenesis, hypercoagulability and plaque permeability. Herein, we report the therapeutic effects of perfluorocarbon core nanoparticles (PFC-NP) conjugated to the thrombin inhibitor D-phenylalanyl-L-prolyl-L-chloromethylketone (PPACK-NP) on vascular barrier integrity and hypercoagulability. Methods and Results: ApoE-/- mice were fed a Western diet for 4 months, and received 3 doses/week of saline or 1 ml/kg PPACK-NP for the final month of feeding. Endothelial barrier integrity was assessed by quantifying the ability of atherosclerotic aortas to take up circulating semipermeable PFC-NP (~250 nm diameter). Whole aortas (arch to iliacs) were excised after 2 hour in vivo exposure to PFC-NP and underwent fluorine magnetic resonance spectroscopy ( 19 F-MRS) to quantify plaque-permeating PFC-NP. 19 F-MRS data revealed a significant decrease in plaque permeability to PFC-NP after PPACK-NP treatment compared to saline control (0.081 ± 0.011 μl PFC-NP/g aorta, N = 5 vs. 0.122 ± 0.014 μl PFC-NP/g aorta, N = 8 for PPACK-NP treated vs. saline control, p = 0.027). To assess hypercoagulability, carotid artery injury was induced photochemically to measure the time to complete occlusion as an index of thrombotic risk. Occlusion times were significantly prolonged with PPACK-NP treatment compared to untreated mice (49.8 ± 6.7 min, N = 5 vs. 26.1 ± 4.6 min, N = 9 for PPACK-NP treated vs. saline control, p = 0.019), indicating a decrease in vessel hypercoagulability after therapeutic intervention. Furthermore, PPACK-NP treatment of human aortic endothelial cells in vitro abrogated thrombin-mediated activation of surface PAR-1 receptors as measured by flow cytometry, suggesting a potential dual role for PPACK-NP in the localized modulation of both thrombosis and PAR-1 signaling. Moreover, this sustained therapeutic benefit is obtained without systemic anticoagulation as all clotting parameters and bleeding times are completely normalized within 60 minutes after i.v. injection. Conclusion: Thrombin inhibition with PPACK-NP is effective in restoring vascular barrier integrity and reducing focal thrombotic risk within a single month without incurring bleeding risk.


2014 ◽  
Vol 12 (5) ◽  
pp. 690-700 ◽  
Author(s):  
J. Sundaram ◽  
S. Keshava ◽  
R. Gopalakrishnan ◽  
C. T. Esmon ◽  
U. R. Pendurthi ◽  
...  

2017 ◽  
Vol 71 (Suppl. 1) ◽  
pp. 11-16 ◽  
Author(s):  
Ravinder Nagpal ◽  
Hariom Yadav

Background: The intestinal epithelial layer is the chief barricade between the luminal contents and the host. A healthy homeostatic intestinal barrier is pivotal for maintaining gastrointestinal health, which impacts the overall health as it safeguards the gut-blood axis and checks gut microbes including potential pathogens from entering into the circulation. Summary: Under healthy milieus, the intestinal barrier is generally very dynamic and effective, with luminal side being heavily infested with a wide variety of gut microbes while the basolateral side remains virtually sterile. However, certain conditions such as abnormal exposure to toxins, drugs, pathogens etc. or a state of hyper-inflammation due to disease conditions may weaken or destabilize the integrity of gut epithelia. A perturbed gut integrity and permeability (“leaky gut”) may lead to microbial (bacterial) translocation, and the eventual leakage of bacteria or their metabolites into the circulation can make the host susceptible to various types of diseases via inducing chronic or acute inflammatory response. Key Message: Given a close association with gut integrity, bacterial translocation and inflammatory responses have recently emerged as a clinically important research field and have unveiled novel aspects of gut microbial ecology and various gastrointestinal, metabolic, and lifestyle diseases. This review aims to describe the significance of a healthy gut barrier integrity and permeability, as well as the factors and consequences associated with a compromised gut barrier, while discussing briefly the dietary approaches including probiotics and prebiotics that could ameliorate gut health by restoring gut environment and barrier integrity, thereby preventing bacterial translocation.


2021 ◽  
Author(s):  
Ben A Calvert ◽  
Erik J Quiroz ◽  
Zareeb Lorenzana ◽  
Ngan Doan ◽  
Seongjae Kim ◽  
...  

In response to viral infection, neutrophils release inflammatory mediators as part of the innate immune response, contributing to pathogen clearance through virus internalization and killing. Pre-existing co-morbidities, correlating to incidence of severe COVID-19, are associated with chronic airway neutrophilia and examination of COVID-19 lung tissue revealed a series of epithelial pathologies associated with infiltration and activation of neutrophils. To determine the impact of neutrophil-epithelial interactions on the infectivity and inflammatory response to SARS-CoV-2 infection, we developed a co-culture model of airway neutrophilia. We discovered that SARS-CoV-2 infection of the airway epithelium alone does not result in a notable release of pro-inflammatory cytokines, however in the presence of neutrophils, the inflammatory response is both polarized and significantly augmented, epithelial barrier integrity in impaired and viral load of the airway epithelium increased. Overall, study reveals a key role for neutrophil-epithelial interactions in determining inflammation, infectivity, and outcomes in response to SARS-CoV-2 infection.


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