PMID- 32458348
OWN - NLM
STAT- MEDLINE
DCOM- 20210715
LR  - 20210715
IS  - 1573-2576 (Electronic)
IS  - 0360-3997 (Linking)
VI  - 43
IP  - 5
DP  - 2020 Oct
TI  - Lin28B Regulates Angiotensin II-Mediated Let-7c/miR-99a MicroRNA Formation 
      Consequently Affecting Macrophage Polarization and Allergic Inflammation.
PG  - 1846-1861
LID - 10.1007/s10753-020-01258-1 [doi]
AB  - Angiotensin-II (Ang-II) receptor plays a role in allergic airway inflammation; 
      however, the underlying mechanism and role of macrophages need better 
      understanding. In the present study, angiotensin-II infusion (1 mug/kg/min) in 
      ovalbumin-induced airway inflammation mice model significantly decreased immune 
      cell infiltration, goblet cell hyperplasia, and eosinophil numbers in lungs. 
      Ang-II infusion increased M1 and decreased M2 macrophage population in 
      bronchoalveolar lavage fluid and respective macrophage markers in lung 
      macrophages. Similarly, in vitro Ang-II treatment in murine bone marrow-derived 
      macrophages (BMDMs) induced M1 and reduced M2 macrophage phenotype with enhanced 
      bactericidal activity. Mechanistically, Ang-II inhibits Let-7c and miR-99a 
      expression in BMDMs and in vivo as well. Lentiviral overexpression of Let-7c and 
      miR-99a miRNAs in BMDMs abrogated Ang-II-induced M1 phenotype activation and 
      promoted M2 phenotype, which is governed by targeting TNFalpha by miR-99a. In lung 
      macrophages, ovalbumin-induced TNFalpha inhibition was rescued after Ang-II 
      treatment. In BMDMs, knockdown of TNFalpha abrogated Ang-II-induced M2 to M1 
      macrophage phenotype switch and associated bactericidal activity. Ang-II affects 
      mature miRNA formation by enhancing Lin28B levels in macrophages in vivo and in 
      vitro. Furthermore, Lin28B knockdown prevented Ang-II-mediated inhibition of 
      mature Let-7c/miR-99a miRNA formation, M2 to M1 macrophage phenotype switch, and 
      increased bactericidal activity. Therefore, present study suggests a role of 
      Lin28B in Ang-II-induced Let-7c/miR-99a miRNA formation that consequently affects 
      TNFalpha production, M1 phenotype activation, and allergic airway inflammation. 
      Graphical Abstract Ovalbumin inhibits LIN28B expression thereby fails to inhibit 
      premature to mature Let-7c/miR-99a miRNA formation. Mature miR-99a miRNA that 
      inhibits TNFalpha consequently promotes M2 polarization and allergic airway 
      inflammation. While Ang-II induces Lin28B, which inhibits Let-7c/miR-99a miRNA 
      processing and mature miRNA formation, this results in increased TNFalpha levels that 
      lead to M1 polarization and allergic airway inflammation inhibition.
FAU - Jaiswal, Anant
AU  - Jaiswal A
AD  - Division of Pharmacology, Council of Scientific and Industrial Research-Central 
      Drug Research Institute (CSIR-CDRI), Lucknow, UP, 226031, India.
FAU - Maurya, Mohita
AU  - Maurya M
AD  - Division of Pharmacology, Council of Scientific and Industrial Research-Central 
      Drug Research Institute (CSIR-CDRI), Lucknow, UP, 226031, India.
FAU - Maurya, Preeti
AU  - Maurya P
AD  - Academy of Scientific and Innovative Research, New Delhi, 110025, India.
FAU - Barthwal, Manoj Kumar
AU  - Barthwal MK
AUID- ORCID: 0000-0001-7574-482X
AD  - Division of Pharmacology, Council of Scientific and Industrial Research-Central 
      Drug Research Institute (CSIR-CDRI), Lucknow, UP, 226031, India. 
      manojbarthwal@cdri.res.in.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Inflammation
JT  - Inflammation
JID - 7600105
RN  - 0 (Lin28b protein, mouse)
RN  - 0 (MIRNlet-7c microRNA, human)
RN  - 0 (MicroRNAs)
RN  - 0 (Mirn99 microRNA, mouse)
RN  - 0 (RNA-Binding Proteins)
RN  - 11128-99-7 (Angiotensin II)
RN  - 9006-59-1 (Ovalbumin)
SB  - IM
MH  - Angiotensin II/*toxicity
MH  - Animals
MH  - Cell Polarity/drug effects/physiology
MH  - Cells, Cultured
MH  - HEK293 Cells
MH  - Humans
MH  - Hypersensitivity/immunology/*metabolism
MH  - Macrophages, Alveolar/drug effects/immunology/*metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - MicroRNAs/antagonists & inhibitors/*biosynthesis
MH  - Ovalbumin/toxicity
MH  - Pneumonia/chemically induced/immunology/metabolism
MH  - RNA-Binding Proteins/*biosynthesis
OTO - NOTNLM
OT  - Let-7c/miR-99a/TNF
OT  - Lin28B
OT  - M1/M2 phenotype
OT  - allergic inflammation
OT  - angiotensin-II
EDAT- 2020/05/28 06:00
MHDA- 2021/07/16 06:00
CRDT- 2020/05/28 06:00
PHST- 2020/05/28 06:00 [pubmed]
PHST- 2021/07/16 06:00 [medline]
PHST- 2020/05/28 06:00 [entrez]
AID - 10.1007/s10753-020-01258-1 [pii]
AID - 10.1007/s10753-020-01258-1 [doi]
PST - ppublish
SO  - Inflammation. 2020 Oct;43(5):1846-1861. doi: 10.1007/s10753-020-01258-1.