Protective Role of Urinary Trypsin Inhibitor in Acute Lung Injury Induced by Lipopolysaccharide

2005 ◽  
Vol 230 (4) ◽  
pp. 281-287 ◽  
Author(s):  
Ken-ichiro Inoue ◽  
Hirohisa Takano ◽  
Rie Yanagisawa ◽  
Miho Sakurai ◽  
Akinori Shimada ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Trypsin Inhibitor ◽  
Inflammatory Diseases ◽  
Lavage Fluid ◽  
Intercellular Adhesion Molecule ◽  
Urinary Trypsin Inhibitor ◽  
Intercellular Adhesion Molecule 1 ◽  
Lung Water ◽  
Lps Challenge

Urinary trypsin inhibitor (UTI), a serine protease inhibitor, has been widely used as a drug for patients with acute inflammatory disorders such as disseminated intravascular coagulation, shock, and pancreatitis. However, direct contribution of UTI to inflammatory diseases has not been established. The present study analyzed acute inflammatory lung injury induced by lipopolysaccharide (LPS) in UTI-deficient (–/–) mice and corresponding wild-type (WT) mice. UTI (–/–) and WT mice were treated intratracheally with vehicle or LPS (125 μg/kg). The cellular profile of bronchoalveolar lavage fluid, lung water content, histology, and expression of proinflammatory molecules in the lung were evaluated. After LPS challenge, both genotypes of mice revealed neutrophilic lung inflammation and pulmonary edema. UTI (–/–) mice, however, showed more prominent infiltration of inflammatory cells and edema than WT mice. After LPS challenge in both genotypes of mice, the lung levels of mRNA and/or protein expression of interleukin-1β, macrophage inflammatory protein-1α, macrophage chemoattractant protein-1, keratinocyte chemoattractant, and intercellular adhesion molecule-1 (ICAM-1) were elevated in both groups, but to a greater extent in UTI (–/–) mice than in WT mice. These results suggest that UTI protects against acute lung injury induced by bacterial endotoxin, at least partly, through the inhibition of the enhanced local expression of proinflammatory cytokines, chemokines, and ICAM-1.

Effects of Urinary Trypsin Inhibitor on Lipopolysaccharide-Induced Acute Lung Injury in Rabbits

Inflammation ◽  
2011 ◽  
Vol 35 (1) ◽  
pp. 176-182 ◽  
Author(s):  
Hong-Beom Bae ◽  
Cheol-Won Jeong ◽  
Mei Li ◽  
Hyung-Seok Kim ◽  
Sang-Hyun Kwak
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Trypsin Inhibitor ◽  
Urinary Trypsin Inhibitor

Antioxidative role of urinary trypsin inhibitor in acute lung injury induced by lipopolysaccharide

2005 ◽  
Author(s):  
Ken-Ichiro Inoue ◽  
Hirohisa Takano ◽  
Rie Yanagisawa ◽  
Miho Sakurai ◽  
Akinori Shimada ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Trypsin Inhibitor ◽  
Urinary Trypsin Inhibitor

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.

scholarly journals Attenuation of Lipopolysaccharide-Induced Acute Lung Injury by Hispolon in Mice, Through Regulating the TLR4/PI3K/Akt/mTOR and Keap1/Nrf2/HO-1 Pathways, and Suppressing Oxidative Stress-Mediated ER Stress-Induced Apoptosis and Autophagy

Nutrients ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1742 ◽  
Author(s):  
Ching-Ying Huang ◽  
Jeng-Shyan Deng ◽  
Wen-Chin Huang ◽  
Wen-Ping Jiang ◽  
Guan-Jhong Huang
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Er Stress ◽  
Anterior Segment ◽  
Signal Transduction Pathway ◽  
Lavage Fluid ◽  
Cell Number ◽  
Lps Challenge ◽  
Induced Apoptosis

The anti-inflammatory effect of hispolon has identified it as one of the most important compounds from Sanghuangporus sanghuang. The research objectives were to study this compound using an animal model by lipopolysaccharide (LPS)-induced acute lung injury. Hispolon treatment reduced the production of the pro-inflammatory mediator NO, TNF-α, IL-1β, and IL-6 induced by LPS challenge in the lung tissues, as well as decreasing their histological alterations and protein content. Total cell number was also reduced in the bronchoalveolar lavage fluid (BALF). Moreover, hispolon inhibited iNOS, COX-2 and IκB-α and phosphorylated IKK and MAPK, while increasing catalase, SOD, GPx, TLR4, AKT, HO-1, Nrf-2, Keap1 and PPARγ expression, after LPS challenge. It also regulated apoptosis, ER stress and the autophagy signal transduction pathway. The results of this study show that hispolon regulates LPS-induced ER stress (increasing CHOP, PERK, IRE1, ATF6 and GRP78 protein expression), apoptosis (decreasing caspase-3 and Bax and increasing Bcl-2 expression) and autophagy (reducing LC3 I/II and Beclin-1 expression). This in vivo experimental study suggests that hispolon suppresses the LPS-induced activation of inflammatory pathways, oxidative injury, ER stress, apoptosis and autophagy and has the potential to be used therapeutically in major anterior segment lung diseases.

Does Urinary Trypsin Inhibitor Have a Role in Acute Lung Injury Induced by Pulmonary Contusion

2014 ◽  
Vol 21 (6) ◽  
pp. 447-452
Author(s):  
Shaohua Wang ◽  
Jin Wang ◽  
Xi Chen ◽  
Zheng Ruan ◽  
Jin Zheng ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Trypsin Inhibitor ◽  
Pulmonary Contusion ◽  
Urinary Trypsin Inhibitor

scholarly journals Urinary Trypsin Inhibitor Attenuates Acute Lung Injury by Improving Endothelial Progenitor Cells Functions

2015 ◽  
Vol 36 (3) ◽  
pp. 1059-1068 ◽  
Author(s):  
Weixin Guo ◽  
Zhihong Li ◽  
Xiaoyun Xie ◽  
Tiehe Qin ◽  
Yan Wu ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Protein Expression ◽  
Trypsin Inhibitor ◽  
Rabbit Model ◽  
Fold Increase ◽  
Tube Formation ◽  
No Production ◽  
Urinary Trypsin Inhibitor ◽  
Phosphorylated Akt

Background: Urinary Trypsin Inhibitor (UTI) is involved in various aspects of tissue repair, regeneration and development. However, the potential role of UTI in protection against acute lung injury (ALI) remains largely unknown. In the present study, we demonstrated that UTI treatment could ameliorate ALI induced by oleic acid (OA) treatment in rabbit model. Methods: Intravenous application of UTI (10000 U/kg/d) significantly improved the pathologies associated with OA-induced ALI. The lungs were stained with hematoxylin and eosin to scored the lung injury. Peripheral blood mononuclear cells were isolated by density gradient centrifugation with Ficoll-Plaque Plus. The proliferation and ability of tube structure formation of EPCs were observed and the level of phosphorylated Akt protein expression and eNOS protein expression were assayed. Results: Consistent with pathological scores, UTI treatment significantly reduced wet/dry ratio of OA injured lungs. A quantification of capillary density revealed that UTI treatment led to about 2 fold increase over uninjured control and about 1.5 fold increase over PBS treatment. The capacity for tube formation of EPCs on ECM gel was significantly reduced in the ALI group and recovered with UTI treatment. Quantification of western blot bands was summarized and showed that UTI treatment activates Akt/eNOS signaling. NO production could contribute to the improvement of EPCs function by UTI treatment. Conclusions: UTI-induced phosphorylation/activation of eNOS and Akt, increases the intracellular level of NO, thereby improving tube formation and proliferation function of EPCs. EPCs function is crucial for re-endothelialization after denuding injuries of arteries.

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