PMID- 25261473
OWN - NLM
STAT- MEDLINE
DCOM- 20150303
LR  - 20211021
IS  - 1550-6606 (Electronic)
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 193
IP  - 9
DP  - 2014 Nov 1
TI  - miR-15a/16 regulates macrophage phagocytosis after bacterial infection.
PG  - 4558-67
LID - 10.4049/jimmunol.1401372 [doi]
AB  - Bacterial infection and its associated sepsis are devastating clinical entities 
      that lead to high mortality and morbidity in critically ill patients. 
      Phagocytosis, along with other innate immune responses, exerts crucial impacts on 
      the outcomes of these patients. MicroRNAs (miRNAs) are a novel class of 
      regulatory noncoding RNAs that target specific mRNAs for modulation of 
      translation and expression of a targeted protein. The roles of miRNAs in host 
      defense against bacterial sepsis remain unclear. We found that bacterial 
      infections and/or bacterial-derived LPS enhanced the level of miR-15a/16 in bone 
      marrow-derived macrophages (BMDMs). Deletion of miR-15a/16 (miR-15a/16(-/-)) in 
      myeloid cells significantly decreased the bacterial infection-associated 
      mortality in sepsis mouse models. Moreover, miR-15a/16 deficiency 
      (miR-15a/16(-/-)) resulted in augmented phagocytosis and generation of 
      mitochondrial reactive oxygen species in BMDMs. Supportively, overexpression of 
      miR-15a/16 using miRNA mimics led to decreased phagocytosis and decreased 
      generation of mitochondrial reactive oxygen species. Mechanistically, deletion of 
      miR-15a/16 upregulated the expression of TLR4 via targeting the principle 
      transcriptional regulator PU.1 locating on the promoter region of TLR4, and 
      further modulated the downstream signaling molecules of TLR4, including Rho 
      GTPase Cdc 42 and TRAF6. In addition, deficiency of miR-15a/16 also facilitated 
      TLR4-mediated proinflammatory cytokine/chemokine release from BMDMs at the 
      initial phase of infections. Taken together, miR-15a/16 altered phagocytosis and 
      bacterial clearance by targeting, at least partially, on the TLR4-associated 
      pathways, subsequently affecting the survival of septic mice.
CI  - Copyright (c) 2014 by The American Association of Immunologists, Inc.
FAU - Moon, Hyung-Geun
AU  - Moon HG
AD  - Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, 
      Harvard Medical School, Boston, MA 02115; and.
FAU - Yang, Jincheng
AU  - Yang J
AD  - Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, 
      Harvard Medical School, Boston, MA 02115; and.
FAU - Zheng, Yijie
AU  - Zheng Y
AD  - Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, 
      Harvard Medical School, Boston, MA 02115; and Department of Hematology, Columbia 
      University, New York, NY 10032.
FAU - Jin, Yang
AU  - Jin Y
AD  - Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, 
      Harvard Medical School, Boston, MA 02115; and yjin@rics.bwh.harvard.edu.
LA  - eng
GR  - R01 GM111313/GM/NIGMS NIH HHS/United States
GR  - R01 HL102076/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20140926
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Cytokines)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (MicroRNAs)
RN  - 0 (Mirn15 microRNA, mouse)
RN  - 0 (Mirn16 microRNA, mouse)
RN  - 0 (Toll-Like Receptor 4)
SB  - IM
MH  - Animals
MH  - Bacterial Infections/*genetics/*immunology/microbiology/mortality
MH  - Cell Survival
MH  - Cytokines/metabolism
MH  - Disease Models, Animal
MH  - Gene Deletion
MH  - Gene Expression
MH  - Lipopolysaccharides/immunology
MH  - Macrophages/*immunology/metabolism/microbiology
MH  - Mice
MH  - Mice, Knockout
MH  - MicroRNAs/*genetics
MH  - Mitochondria/metabolism
MH  - Phagocytosis/*genetics/*immunology
MH  - Sepsis/genetics/immunology/microbiology
MH  - Signal Transduction
MH  - Toll-Like Receptor 4/metabolism
PMC - PMC4216178
MID - NIHMS626477
EDAT- 2014/09/28 06:00
MHDA- 2015/03/04 06:00
PMCR- 2015/11/01
CRDT- 2014/09/28 06:00
PHST- 2014/09/28 06:00 [entrez]
PHST- 2014/09/28 06:00 [pubmed]
PHST- 2015/03/04 06:00 [medline]
PHST- 2015/11/01 00:00 [pmc-release]
AID - jimmunol.1401372 [pii]
AID - 10.4049/jimmunol.1401372 [doi]
PST - ppublish
SO  - J Immunol. 2014 Nov 1;193(9):4558-67. doi: 10.4049/jimmunol.1401372. Epub 2014 
      Sep 26.