Lipopolysaccharide-induced CCN1 production enhances interleukin-6 secretion in bronchial epithelial cells

Lin Shi,Chengshui Chen,Zhaojian Ying,Dongxiang Ji,Nian Dong,Xiaomin Huang,Xiangdong Wang

doi:10.1007/s10565-017-9401-1

Abstract

Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is a clinical complication caused by primary or secondary lung injury, as well as by systemic inflammation. Researches regarding molecular pathophysiology of ALI/ARDS are immerging with an ultimate aim towards developing prognostic molecular biomarkers and molecule-based therapy. However, the molecular mechanisms concerning ALI/ARDS are still not completely understood. The purpose of the present study was to identify a crucial role of CCN1 in inflammatory microenvironment during ALI/ARDS and focus on a potential communication between CCN1 and interleukin-6 (IL-6) in the airway epithelial cells. Our data illustrated that the expression levels of CCN1 and IL-6 in bronchoalveolar lavage fluid (BALF) in a lipopolysaccharide (LPS)-induced ALI mouse model were significantly elevated and the pulmonary expression of CCN1 was restricted to bronchial epithelial cells. Interestingly, both endogenous and exogenous CCN1 stimulated IL-6 production in vitro. Furthermore, LPS-induced IL-6 production in a bronchial epithelial cell line was blocked by CCN siRNA whereas CCN1 induced by LPS was sensitive to PI3K inhibition. Together, our data indicate a linear signal pathway, LPS-CCN1-IL-6, existing in bronchial epithelial cells after LPS exposure. This finding may represent an additional mechanism and a novel target for development of therapy and biomarker on ALI/ARDS.

Highlights

Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is characterized by an excessive inflammatory response and damage of the alveolar epithelialcapillary barrier, associated with different cells and inflammatory mediators (Chen et al 2016)
We examined gene and protein expression of CCN1 in mice intratracheally pretreated with LPS or PBS
Constitutive expression of CCN1 protein was found in the lung tissues and bronchoalveolar lavage fluid (BALF) of ALI mice (Fig. 2b, c)

Summary

Introduction

Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is characterized by an excessive inflammatory response and damage of the alveolar epithelialcapillary barrier, associated with different cells and inflammatory mediators (Chen et al 2016). It has been reported that airway epithelial cells can act as the receptor to defend against inflammatory stimuli and antigens, and induce secondary inflammatory responses and systemic reactions in ALI/ARDS through secreting a variety of pro-inflammatory cytokines and chemokines (Wang et al 2007). As an early stress response gene product, CCN1 is expressed in a wide range of cells including airway epithelial cells (Jin et al 2009; Jin et al 2005). It can be induced by bacterial and viral infections, or stimuli like TNF-α and IL-1 (Chen and Lau 2009). The precise biological function of the new inflammatory mediator CCN1 in the setting of ALI/ARDS remains to be elucidated

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Results