PMID- 31434287
OWN - NLM
STAT- MEDLINE
DCOM- 20200406
LR  - 20201029
IS  - 2073-4409 (Electronic)
IS  - 2073-4409 (Linking)
VI  - 8
IP  - 8
DP  - 2019 Aug 20
TI  - DROSHA-Dependent AIM2 Inflammasome Activation Contributes to Lung Inflammation 
      during Idiopathic Pulmonary Fibrosis.
LID - 10.3390/cells8080938 [doi]
LID - 938
AB  - 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)-1beta 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.
FAU - Cho, Soo Jung
AU  - Cho SJ
AD  - Joan and Sanford I. Weill Department of Medicine, Weill Cornell Medical College, 
      New York-Presbyterian Hospital, New York, NY 10011, USA.
AD  - Division of Pulmonary and Critical Care Medicine, Weill Cornell Medical College, 
      New York, NY 10011, USA.
FAU - Hong, Kyoung Sook
AU  - Hong KS
AD  - Joan and Sanford I. Weill Department of Medicine, Weill Cornell Medical College, 
      New York-Presbyterian Hospital, New York, NY 10011, USA.
AD  - Division of Pulmonary and Critical Care Medicine, Weill Cornell Medical College, 
      New York, NY 10011, USA.
AD  - Department of Surgery and Critical Care Medicine, Ewha Womans University College 
      of Medicine, Seoul 05505, Korea.
FAU - Jeong, Ji Hun
AU  - Jeong JH
AD  - Department of Integrated Biomedical Science, Soonchunhyang Institute of Medi-bio 
      Science (SIMS), Soonchunhyang University, Cheonan-si 31151, Korea.
FAU - Lee, Mihye
AU  - Lee M
AD  - Department of Integrated Biomedical Science, Soonchunhyang Institute of Medi-bio 
      Science (SIMS), Soonchunhyang University, Cheonan-si 31151, Korea.
FAU - Choi, Augustine M K
AU  - Choi AMK
AD  - Joan and Sanford I. Weill Department of Medicine, Weill Cornell Medical College, 
      New York-Presbyterian Hospital, New York, NY 10011, USA.
AD  - Division of Pulmonary and Critical Care Medicine, Weill Cornell Medical College, 
      New York, NY 10011, USA.
FAU - Stout-Delgado, Heather W
AU  - Stout-Delgado HW
AD  - Joan and Sanford I. Weill Department of Medicine, Weill Cornell Medical College, 
      New York-Presbyterian Hospital, New York, NY 10011, USA.
AD  - Division of Pulmonary and Critical Care Medicine, Weill Cornell Medical College, 
      New York, NY 10011, USA.
FAU - Moon, Jong-Seok
AU  - Moon JS
AUID- ORCID: 0000-0002-2537-7854
AD  - Department of Integrated Biomedical Science, Soonchunhyang Institute of Medi-bio 
      Science (SIMS), Soonchunhyang University, Cheonan-si 31151, Korea. 
      jongseok81@sch.ac.kr.
LA  - eng
GR  - K08 HL138285/HL/NHLBI NIH HHS/United States
GR  - P01 HL114501/HL/NHLBI NIH HHS/United States
GR  - R01 AG052530/AG/NIA NIH HHS/United States
GR  - R01 AG056699/AG/NIA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20190820
PL  - Switzerland
TA  - Cells
JT  - Cells
JID - 101600052
RN  - 0 (AIM2 protein, human)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Inflammasomes)
RN  - EC 3.1.26.3 (DROSHA protein, human)
RN  - EC 3.1.26.3 (Ribonuclease III)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Animals
MH  - Cells, Cultured
MH  - Chronic Disease
MH  - DNA-Binding Proteins/*metabolism
MH  - Female
MH  - Humans
MH  - Idiopathic Pulmonary Fibrosis/*pathology
MH  - Inflammasomes/*metabolism
MH  - Macrophages/*metabolism/pathology
MH  - Macrophages, Alveolar/*metabolism/pathology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Middle Aged
MH  - *Pneumonia/metabolism/pathology
MH  - Ribonuclease III/*physiology
PMC - PMC6721825
OTO - NOTNLM
OT  - AIM2 inflammasome
OT  - DROSHA
OT  - idiopathic pulmonary fibrosis
OT  - miRNA
COIS- A.M.K.C. is a cofounder, stock holder and serves on the Scientific Advisory Board 
      for Proterris, which develops therapeutic uses for carbon monoxide. A.M.K.C. also 
      has a use patent on CO. He served on the TEVA Advisory Board meeting as a 
      consultant on July 12-13, 2018. The spouse of M.E.C. is a co-founder, shareholder 
      and serves on the Scientific Advisory Board of Proterris, Inc.
EDAT- 2019/08/23 06:00
MHDA- 2020/04/09 06:00
PMCR- 2019/08/01
CRDT- 2019/08/23 06:00
PHST- 2019/07/22 00:00 [received]
PHST- 2019/08/18 00:00 [revised]
PHST- 2019/08/19 00:00 [accepted]
PHST- 2019/08/23 06:00 [entrez]
PHST- 2019/08/23 06:00 [pubmed]
PHST- 2020/04/09 06:00 [medline]
PHST- 2019/08/01 00:00 [pmc-release]
AID - cells8080938 [pii]
AID - cells-08-00938 [pii]
AID - 10.3390/cells8080938 [doi]
PST - epublish
SO  - Cells. 2019 Aug 20;8(8):938. doi: 10.3390/cells8080938.