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DROSHA-Dependent AIM2 Inflammasome Activation Contributes to Lung Inflammation during Idiopathic Pulmonary Fibrosis
- Title
- DROSHA-Dependent AIM2 Inflammasome Activation Contributes to Lung Inflammation during Idiopathic Pulmonary Fibrosis
- Authors
- Cho, Soo Jung; Hong, Kyoung Sook; Jeong, Ji Hun; Lee, Mihye; Choi, Augustine M. K.; Stout-Delgado, Heather W.; Moon, Jong-Seok
- Ewha Authors
- 홍경숙
- SCOPUS Author ID
- 홍경숙
- Issue Date
- 2019
- Journal Title
- CELLS
- ISSN
- 2073-4409
- Citation
- CELLS vol. 8, no. 8
- Keywords
- DROSHA; miRNA; AIM2 inflammasome; idiopathic pulmonary fibrosis
- Publisher
- MDPI
- Indexed
- SCIE; SCOPUS
- Document Type
- Article
- Abstract
- Idiopathic pulmonary fibrosis (IPF) has been linked to chronic lung inflammation. Drosha ribonuclease III (DROSHA), a class 2 ribonuclease III enzyme, plays a key role in microRNA (miRNA) biogenesis. However, the mechanisms by which DROSHA affects the lung inflammation during idiopathic pulmonary fibrosis (IPF) remain unclear. Here, we demonstrate that DROSHA regulates the absent in melanoma 2 (AIM2) inflammasome activation during idiopathic pulmonary fibrosis (IPF). Both DROSHA and AIM2 protein expression were elevated in alveolar macrophages of patients with IPF. We also found that DROSHA and AIM2 protein expression were increased in alveolar macrophages of lung tissues in a mouse model of bleomycin-induced pulmonary fibrosis. DROSHA deficiency suppressed AIM2 inflammasome-dependent caspase-1 activation and interleukin (IL)-1 beta and IL-18 secretion in primary mouse alveolar macrophages and bone marrow-derived macrophages (BMDMs). Transduction of microRNA (miRNA) increased the formation of the adaptor apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) specks, which is required for AIM2 inflammasome activation in BMDMs. Our results suggest that DROSHA promotes AIM2 inflammasome activation-dependent lung inflammation during IPF.
- DOI
- 10.3390/cells8080938
- Appears in Collections:
- 의료원 > 의료원 > Journal papers
- Files in This Item:
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DROSHA-Dependent AIM2.pdf(4.01 MB)
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