High molecular weight hyaluronan attenuates fine particulate matter-induced acute lung injury through inhibition of ROS-ASK1-p38/JNK-mediated epithelial apoptosis

Environ Toxicol Pharmacol. 2018 Apr:59:190-198. doi: 10.1016/j.etap.2018.03.020. Epub 2018 Mar 30.

Abstract

Inhalation of fine particulate matter (PM2.5) is asscoiated with lung injury. High molecular weight hyaluronan (HMW-HA) is an essential constituent of extracellular matrix (ECM), exhibiting anti-oxidative and anti-inflammatory properties when administered by injection, inhalation, nebulization or gene delivery of HA synthases. The aim of the present study is to determine whether HMW-HA alleviates PM2.5-induced acute lung injury (ALI) and investigate the underlying mechanisms. We observed that HMW-HA suppressed pathological injury, inflammation, oxidative stress, edema and epithelial damage caused by PM2.5 in the lungs of the rats. The protective mechanism of HMW-HA was further explored in vitro. The results elucidated that reactive oxygen species (ROS) was involved in PM2.5-induced cell apoptosis, and HMW-HA mitigated the oxidative potential of PM2.5, subsequently inhibiting phosphorylation of ASK1 at Thr845, downstream phosphorylation of p38 and JNK, and eventual apoptosis. Our study indicates that HMW-HA is a promising strategy in the prevention of PM2.5-induced pulmonary damage.

Keywords: Fine particulate matter; Hyaluronan; Lung injury; Reactive oxygen species.

MeSH terms

  • Acute Lung Injury / chemically induced
  • Acute Lung Injury / drug therapy*
  • Animals
  • Anti-Inflammatory Agents / chemistry
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use*
  • Apoptosis / drug effects
  • Bronchoalveolar Lavage Fluid / chemistry
  • Bronchoalveolar Lavage Fluid / cytology
  • Cell Count
  • Cell Line
  • Cell Survival / drug effects
  • Humans
  • Hyaluronic Acid / chemistry
  • Hyaluronic Acid / pharmacology
  • Hyaluronic Acid / therapeutic use*
  • Interleukin-1beta / metabolism
  • Lung / drug effects
  • Lung / metabolism
  • Lung / pathology
  • MAP Kinase Kinase 4 / metabolism
  • MAP Kinase Kinase Kinase 5 / metabolism
  • Male
  • Molecular Weight
  • Nitric Oxide / metabolism
  • Particulate Matter
  • Rats, Sprague-Dawley
  • Reactive Oxygen Species / metabolism
  • Tumor Necrosis Factor-alpha / metabolism
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Anti-Inflammatory Agents
  • IL1B protein, rat
  • Interleukin-1beta
  • Particulate Matter
  • Reactive Oxygen Species
  • Tumor Necrosis Factor-alpha
  • Nitric Oxide
  • Hyaluronic Acid
  • p38 Mitogen-Activated Protein Kinases
  • MAP Kinase Kinase Kinase 5
  • MAP Kinase Kinase 4