DROSHA-Dependent AIM2 Inflammasome Activation Contributes to Lung Inflammation during Idiopathic Pulmonary Fibrosis

Soo Jung Cho1,2, Kyoung Sook Hong1,2,3, Ji Hun Jeong4

  • 1Joan and Sanford I. Weill Department of Medicine, Weill Cornell Medical College, New York-Presbyterian Hospital, New York, NY 10011, USA.

Cells
|August 23, 2019
PubMed

Insights

Drosha ribonuclease III (DROSHA) regulates the absent in melanoma 2 (AIM2) inflammasome, a key driver of lung inflammation in idiopathic pulmonary fibrosis (IPF). This study reveals DROSHA

Area of Science:

  • Molecular Biology
  • Immunology
  • Pulmonary Medicine

Background:

  • Idiopathic pulmonary fibrosis (IPF) involves chronic lung inflammation.
  • Drosha ribonuclease III (DROSHA) is crucial for microRNA (miRNA) biogenesis.
  • The role of DROSHA in IPF-related lung inflammation is not fully understood.

Purpose of the Study:

  • To investigate the role of DROSHA in regulating absent in melanoma 2 (AIM2) inflammasome activation in idiopathic pulmonary fibrosis (IPF).
  • To elucidate the mechanisms by which DROSHA influences lung inflammation in IPF.

Main Methods:

  • Assessed DROSHA and AIM2 protein expression in alveolar macrophages from IPF patients and a mouse model of bleomycin-induced pulmonary fibrosis.
  • Evaluated the impact of DROSHA deficiency on AIM2 inflammasome activation, caspase-1 cleavage, and cytokine secretion (IL-1β, IL-18) in macrophages.
  • Investigated the effect of miRNA transduction on ASC speck formation and AIM2 inflammasome activation.

Main Results:

  • Elevated DROSHA and AIM2 protein levels were observed in alveolar macrophages of IPF patients and in a mouse model.
  • DROSHA deficiency attenuated AIM2 inflammasome activation, caspase-1 cleavage, and IL-1β/IL-18 secretion.
  • miRNA transduction promoted ASC speck formation, a prerequisite for AIM2 inflammasome activation.

Conclusions:

  • DROSHA plays a significant role in promoting AIM2 inflammasome-dependent lung inflammation in IPF.
  • Targeting the DROSHA-AIM2 inflammasome pathway may offer therapeutic strategies for IPF.

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