Cigarette smoke extract-induced p120-mediated NF-κB activation in human epithelial cells is dependent on the RhoA/ROCK pathway.

Chao Zhang,Shenghui Qin,Renliang Wu,Naping Li,Lingzhi Qin,Xi Wang,Liwei Liu,Wenjia Sun,Xiyu Li

doi:10.1038/srep23131

Abstract

Cigarette smoke exposure is a major cause of chronic obstructive pulmonary disease (COPD), but the underlying molecular inflammatory mechanisms remain poorly understood. Previous studies have found that smoke disrupts cell-cell adhesion by inducing epithelial barrier damage to the adherens junction proteins, primarily E-cadherin (E-cad) and p120-catenin (p120). Recently, the anti-inflammatory role of p120 has drawn increasing attention. In this study, we demonstrate that p120 has a role in the cigarette smoke extract-induced inflammatory response, presumably by regulating NF-κB signaling activation. Mechanistically, we show that p120-mediated NF-κB signaling activation in airway epithelial inflammation is partially RhoA dependent and is independent of E-cad. These results provide novel evidence for the role of p120 in the anti-inflammatory response.

Highlights

Cigarette smoking is a major cause of chronic obstructive pulmonary disease (COPD), which is one of the most important causes of morbidity and mortality in the world
P120 and RhoA/ROCK are shown to be involved in inflammation and inflammation-related diseases; we hypothesize that p120 might play an important role in cigarette smoke extract (CSE)-induced airway injury through the NF-κ B signaling pathway via the RhoA/ROCK axis
We demonstrated that p120 plays a role in the cigarette smoke-induced inflammatory response presumably by regulating the RhoA-NF-κ B axis

Summary

Introduction

Cigarette smoking is a major cause of chronic obstructive pulmonary disease (COPD), which is one of the most important causes of morbidity and mortality in the world. A persistent increase in airway epithelial permeability occurs in smokers and individuals exposed to secondhand smoke[2,3] where the epithelial barrier is disrupted and the subepithelial tissue gets directly exposed to reactive chemicals and oxidants/free radicals[4,5] This insult triggers an inflammatory response that, if sustained, can lead to structural epithelial abnormalities such as remodeling and mucous metaplasia[6]; both of which are hallmarks of COPD and asthma. Our previous research showed that p120 acts as an anti-inflammatory mediator in LPS-stimulated and mechanical scratch-stimulated bronchial epithelial cells (BECs) by modulating NF-κ B signaling[16,17,18]. 15% CSE, which was the maximum concentration that did not cause a significant change in cell viability, was chosen for the following experiments

Methods

Findings

Conclusion