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

Yi-Chen Lee,Yen-Hsu Chen,Stephen Hu,Chin Hsu,Chun-Yu Lin,Shyng-Shiou Yuan,Yu-Han Su,Wen-Chin Chiu,Yen-Yun Wang

doi:10.3390/ijms20071678

Abstract

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.

Highlights

Acute respiratory distress syndrome (ARDS) is a severe form of acute lung injury (ALI) that is characterized by severe lung tissue inflammation, reduced gas exchange, and, acute hypoxemic respiratory failure [1,2]
Since serum visfatin was elevated in Acute lung injury (ALI) patients, we further evaluated the in vivo activity of visfatin in mouse models of ALI, including LPS model and Colon ascendens stent peritonitis (CASP) model [36,37]
We further investigated the in vivo regulation of visfatin protein in ALI mouse models

Summary

Introduction

Acute respiratory distress syndrome (ARDS) is a severe form of acute lung injury (ALI) that is characterized by severe lung tissue inflammation, reduced gas exchange, and, acute hypoxemic respiratory failure [1,2]. Recent studies showed that ALI/ARDS increased the release of proinflammatory cytokines, such as tumor necrosis factor (TNF-α), interleukin (IL)-1β, IL-6, and IL-8 from immune cells [15,16], and increased the permeability of the alveolar–capillary barrier [8,17]. These phenomena indicate that acute inflammation plays an important role in the ALI/ARDS process. Developing more effective strategies to inhibit inflammatory responses and identifying new diagnostic and therapeutic targets are critical for the improvement of patient outcomes

Methods

Results

Conclusion