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

PLoS One. 2017 Jan 3;12(1):e0169100. doi: 10.1371/journal.pone.0169100. eCollection 2017.

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.

MeSH terms

  • Animals
  • Blood Gas Analysis
  • Bronchoalveolar Lavage Fluid
  • CD8-Positive T-Lymphocytes / metabolism
  • Chemokine CXCL10 / antagonists & inhibitors*
  • Chemokine CXCL10 / chemistry*
  • Chemokine CXCL11 / metabolism
  • Chemokine CXCL9 / metabolism
  • Disease Models, Animal
  • Inflammation
  • Intercellular Adhesion Molecule-1 / metabolism
  • Interferon-gamma / metabolism
  • Interleukin-6 / metabolism
  • Ligands
  • Lipopolysaccharides
  • Male
  • Rats
  • Rats, Wistar
  • Receptors, CXCR3 / metabolism
  • Respiratory Distress Syndrome / chemically induced
  • Respiratory Distress Syndrome / drug therapy*

Substances

  • CXCL9 protein, rat
  • Chemokine CXCL10
  • Chemokine CXCL11
  • Chemokine CXCL9
  • Cxcl10 protein, rat
  • Cxcl11 protein, rat
  • Cxcr3 protein, rat
  • ICAM1 protein, rat
  • Interleukin-6
  • Ligands
  • Lipopolysaccharides
  • Receptors, CXCR3
  • Intercellular Adhesion Molecule-1
  • Interferon-gamma

Grant support

This work was supported by National Science and Technology Major Project of China (No.2015ZX09J15105-004). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.