PMID- 27113449
OWN - NLM
STAT- MEDLINE
DCOM- 20170410
LR  - 20181113
IS  - 1573-6881 (Electronic)
IS  - 0145-479X (Linking)
VI  - 48
IP  - 3
DP  - 2016 Jun
TI  - MiR-221 promotes IgE-mediated activation of mast cells degranulation by 
      PI3K/Akt/PLCgamma/Ca(2+) pathway.
PG  - 293-9
LID - 10.1007/s10863-016-9659-7 [doi]
AB  - Mast cells play a pivotal role in the immediate reaction in asthma. In a previous 
      study, it was found that MicroRNA-221 (miR-221) was associated with asthma. 
      Hence, in the present study, the role and the potential mechanisms of miR-221 on 
      immunoglobulin E (IgE)-mediated activation of mast cells degranulation were 
      investigated. MiR-221 expression was first quantified by qRT-PCR in IgE-mediated 
      activation of mast cells. RBL-2H3 cells were then transfected with miR-221 mimic 
      or miR-221 inhibitor, the IgE-mediated degranulation was detected in mast cells. 
      The influence of miR-221 on expression of phospholipase C gamma (PLCgamma1), p-PLCgamma1, 
      protein kinase B (Akt), phospho-Akt (p-Akt), inhibitor of kappa B (IkappaB-alpha), and 
      phospho-IkappaB-alpha (p-IkappaB-alpha) were examined by Western blot, whereas free calcium ion 
      (Ca(2+)) level was measured by flow cytometry and NF-kappaB expression was determined 
      by EMSA. Phosphoinositide 3-kinase (PI3K)-inhibitor (LY294002) and 
      NF-kappaB-inhibitor [pyrrolidine dithiocarbamate (PDTC)] were used to investigate the 
      role of PI3K/Akt pathway and NF-kappaB in miR-221 promoting IgE-mediated activation 
      of mast cells degranulation. The expression of miR-221 was upregulated in 
      IgE-mediated activation of mast cells, and it was overexpressed in miR-221 mimic 
      transfected cells. The degranulation was found to be significantly increased in 
      miR-221 overexpressed cells while it was found to be significantly decreased in 
      miR-221 downregulated cells. The expression of p-PLCgamma1, p-Akt, p-IkappaB-alpha as well as 
      NF-kappaB and Ca(2+) release were increased in miR-221 overexpressed cells. 
      PI3K-inhibitor (LY294002) could rescue the promotion of degranulation caused by 
      miR-221 in IgE-mediated activation of mast cells. However, NF-kappaB-inhibitor (PDTC) 
      could not rescue the promotion of degranulation caused by miR-221 in IgE-mediated 
      activation of mast cells. MiR-221 promotes IgE-mediated activation of mast cells 
      degranulation by PI3K/Akt/PLCgamma/Ca(2+) signaling pathway, in a non-NF-kappaB dependent 
      manner.
FAU - Xu, Hong
AU  - Xu H
AD  - Department of Respiratory Medicine, Nanjing Children's Hospital Affiliated to 
      Nanjing Medical University, Nanjing, China.
FAU - Gu, Li-Na
AU  - Gu LN
AD  - Department of Respiratory Medicine, Nanjing Children's Hospital Affiliated to 
      Nanjing Medical University, Nanjing, China.
FAU - Yang, Qian-Yuan
AU  - Yang QY
AD  - Department of Respiratory Medicine, Nanjing Children's Hospital Affiliated to 
      Nanjing Medical University, Nanjing, China.
FAU - Zhao, De-Yu
AU  - Zhao DY
AD  - Department of Respiratory Medicine, Nanjing Children's Hospital Affiliated to 
      Nanjing Medical University, Nanjing, China. zhaodeyu988@126.com.
FAU - Liu, Feng
AU  - Liu F
AD  - Department of Respiratory Medicine, Nanjing Children's Hospital Affiliated to 
      Nanjing Medical University, Nanjing, China. axsliu@163.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160425
PL  - United States
TA  - J Bioenerg Biomembr
JT  - Journal of bioenergetics and biomembranes
JID - 7701859
RN  - 0 (MIRN221 microRNA, rat)
RN  - 0 (MicroRNAs)
RN  - 0 (NF-kappa B)
RN  - 37341-29-0 (Immunoglobulin E)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 3.1.4.3 (Phospholipase C gamma)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Animals
MH  - Calcium/metabolism
MH  - Cell Degranulation/*drug effects
MH  - Cell Line
MH  - Humans
MH  - Immunoglobulin E/immunology
MH  - Mast Cells
MH  - MicroRNAs/antagonists & inhibitors/genetics/*immunology
MH  - NF-kappa B/metabolism
MH  - Phosphatidylinositol 3-Kinases/*metabolism
MH  - Phospholipase C gamma/metabolism
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Rats
MH  - Rats, Wistar
MH  - *Signal Transduction/drug effects
MH  - Transfection
OTO - NOTNLM
OT  - Degranulation
OT  - Mast cell
OT  - MiR-221
OT  - PI3K/Akt pathway
OT  - PLCgamma/Ca2+ pathway
EDAT- 2016/04/27 06:00
MHDA- 2017/04/11 06:00
CRDT- 2016/04/27 06:00
PHST- 2015/09/23 00:00 [received]
PHST- 2016/03/28 00:00 [accepted]
PHST- 2016/04/27 06:00 [entrez]
PHST- 2016/04/27 06:00 [pubmed]
PHST- 2017/04/11 06:00 [medline]
AID - 10.1007/s10863-016-9659-7 [pii]
AID - 10.1007/s10863-016-9659-7 [doi]
PST - ppublish
SO  - J Bioenerg Biomembr. 2016 Jun;48(3):293-9. doi: 10.1007/s10863-016-9659-7. Epub 
      2016 Apr 25.