CXCL10/IP-10 Neutralization Can Ameliorate Lipopolysaccharide-Induced Acute Respiratory Distress Syndrome in Rats.

Shan Lang,Xuning Wang,Libing Li,Yongjiu Xiao,Mingyue Zhang,Junping Sun,Xinying Xue,Jianxin Wang,Ting Ao,Bernhard Ryffel

doi:10.1371/journal.pone.0169100

Shan Lang, Xuning Wang + Show 8 more

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https://doi.org/10.1371/journal.pone.0169100

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Journal: PloS one	Publication Date: Jan 3, 2017
Citations: 62	License type: CC BY 4.0

Affiliation: Chinese PLA General Hospital

Abstract

The role of C-X-C motif chemokine 10 (CXCL10), a pro-inflammatory factor, in the development of acute respiratory distress syndrome (ARDS) remains unclear. In this study, we explored the role of CXCL10 and the effect of CXCL10 neutralization in lipopolysaccharide (LPS)-induced ARDS in rats. The expression of CXCL10 and its receptor chemokine receptor 3(CXCR3) increased after LPS induction. Moreover, neutralization of CXCL10 ameliorated the severity of ARDS by reducing pulmonary edema, inhibiting the release of inflammatory mediators (IFN-γ, IL-6 and ICAM-1) and limiting inflammatory cells (neutrophils, macrophages, CD8+ T cells) influx into the lung, with a reduction in CXCR3 expression in neutrophils and macrophages. Therefore, CXCL10 could be a potential therapeutic target in LPS-induced ARDS.

Highlights

Acute respiratory distress syndrome (ARDS) is a fatal disease triggered by multiple conditions including severe sepsis and pneumonia [1, 2]
We examined whether CXCL10 neutralization could ameliorate the severity of ARDS
As the majority of leukocytes in Bronchoalveolar lavage fluid (BALF) after LPS induction were neutrophils and macrophages, we investigated the proportion of CXCR3 positivity in neutrophils and macrophages

Summary

Introduction

Acute respiratory distress syndrome (ARDS) is a fatal disease triggered by multiple conditions including severe sepsis and pneumonia [1, 2]. Previous studies have shown that ARDS is associated with a high production of pro-inflammatory cytokines and chemokines, such as TNF-α, IL-1β, and IL-6 [6, 7]. Neutrophils migration to the lung is mediated by various factors, among which chemokines and cell adhesion molecules are considered the most important [10]. The C-X-C motif chemokine10(CXCL10), known as interferon-γ inducible protein 10 (IP-10), is a chemokine that modulates innate and adaptive immune responses by recruiting inflammatory cells (i.e., neutrophils, T lymphocytes and NK cells) to the sites of inflammation [11]. By binding to its receptor CXCR3, CXCL10 can induce chemotaxis, apoptosis, cell growth and angiostasis [12]. Previous studies have shown that chemokines and their receptors play an essential role in various infectious diseases [13].

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