Fibroblast growth factor 10 alleviates particulate matter-induced lung injury by inhibiting the HMGB1-TLR4 pathway

Aging (Albany NY). 2020 Jan 20;12(2):1186-1200. doi: 10.18632/aging.102676. Epub 2020 Jan 20.

Abstract

Exposure to particulate matter (PM) is associated with increased incidence of respiratory diseases. The present study aimed to investigate the roles of fibroblast growth factor 10 (FGF10) in PM-induced lung injury. Mice were intratracheally instilled with FGF10 or phosphate-buffered saline at one hour before instillation of PM for two consecutive days. In addition, the anti-inflammatory impact of FGF10 in vitro and its effect on the high-mobility group box 1 (HMGB1)-toll-like receptor 4 (TLR4) pathway was investigated. It was found that PM exposure is associated with increased inflammatory cell infiltration into the lung and increased vascular protein leakage, while FGF10 pretreatment attenuated both of these effects. FGF10 also decreased the PM-induced expression of interleukin (IL)-6, IL-8, tumor necrosis factor-α and HMGB1 in murine bronchoalveolar lavage fluid and in the supernatants of human bronchial epithelial cells exposed to PM. FGF10 exerted anti-inflammatory and cytoprotective effects by inhibiting the HMGB1-TLR4 pathway. These results indicate that FGF10 may have therapeutic values for PM-induced lung injury.

Keywords: FGF10; HMGB1; TLR4; inflammation; lung injury; particulate matter.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers
  • Biopsy
  • Cell Death
  • Cytokines / metabolism
  • Disease Susceptibility
  • Fibroblast Growth Factor 10 / genetics
  • Fibroblast Growth Factor 10 / metabolism*
  • Gene Expression
  • Gene Knockdown Techniques
  • HMGB1 Protein / genetics
  • HMGB1 Protein / metabolism*
  • Humans
  • Immunohistochemistry
  • Lung Injury / etiology*
  • Lung Injury / metabolism*
  • Lung Injury / pathology
  • Particulate Matter / adverse effects*
  • Respiratory Mucosa / metabolism
  • Respiratory Mucosa / pathology
  • Signal Transduction
  • Toll-Like Receptor 4 / genetics
  • Toll-Like Receptor 4 / metabolism*

Substances

  • Biomarkers
  • Cytokines
  • Fibroblast Growth Factor 10
  • HMGB1 Protein
  • Particulate Matter
  • TLR4 protein, human
  • Toll-Like Receptor 4