Ghrelin alleviates traumatic brain injury-induced acute lung injury through pyroptosis/NF-κB pathway

Int Immunopharmacol. 2020 Feb:79:106175. doi: 10.1016/j.intimp.2019.106175. Epub 2020 Jan 6.

Abstract

Acute lung injury (ALI) is one of the severe complications in patients with traumatic brain injury (TBI), contributing to the high mortality. Ghrelin has protective effects against various inflammatory diseases, but the effects of Ghrelin on TBI-induced ALI and its mechanisms remain unknown. In this study, Ghrelin administration was performed on the mice with TBI, then histological change in cortex and lung tissues, lung vascular permeability and macrophage number in bronchoalveolar lavage fluid (BALF) were examined, respectively. Simultaneously, the alterations of proinflammatory factors and pyroptosis-related proteins in lung tissues were detected. As a result, TBI-induced ALI was ameliorated after Ghrelin treatment, which was demonstrated by improved histology, reduced lung vascular permeability, and peripheral macrophage number. Furthermore, Ghrelin decreased the mRNA levels of proinflammatory factors (IL-1β, IL-6, TNF-α and IL-18), the protein levels of pyroptosis-related proteins (NLRP3, Caspase1-P20, HMGB1 and Gasdermin D), and the phosphorylation levels of NF-κB in lung tissues. These results showed that Ghrelin attenuating TBI-induced ALI might be via ameliorating inflammasome-induced pyroptosis by blocking NF-κB signal, which are important for the prevention and treatment of TBI-induced ALI.

Keywords: Acute lung injury; Inflammation; NF-κB pathway; Pyroptosis; Traumatic brain injury.

MeSH terms

  • Acute Lung Injury / metabolism*
  • Animals
  • Brain Injuries, Traumatic / metabolism*
  • Cytokines / metabolism
  • Ghrelin / metabolism*
  • Humans
  • Inflammation Mediators / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • NF-kappa B / metabolism
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism
  • Phosphorylation
  • Pyroptosis
  • Signal Transduction

Substances

  • Cytokines
  • Ghrelin
  • Inflammation Mediators
  • NF-kappa B
  • NLR Family, Pyrin Domain-Containing 3 Protein