PMID- 29397306
OWN - NLM
STAT- MEDLINE
DCOM- 20190520
LR  - 20190520
IS  - 1477-2566 (Electronic)
IS  - 1465-3249 (Linking)
VI  - 20
IP  - 3
DP  - 2018 Mar
TI  - Anti-inflammatory roles of mesenchymal stromal cells during acute Streptococcus 
      pneumoniae pulmonary infection in mice.
PG  - 302-313
LID - S1465-3249(18)30009-4 [pii]
LID - 10.1016/j.jcyt.2018.01.003 [doi]
AB  - BACKGROUND: Pneumonia is the fourth leading cause of death worldwide, and 
      Streptococcus pneumoniae is the most commonly associated pathogen. Increasing 
      evidence suggests that mesenchymal stromal cells (MSCs) have anti-inflammatory 
      roles during innate immune responses such as sepsis. However, little is known 
      about the effect of MSCs on pneumococcal pneumonia. METHODS: Bone marrow-derived 
      macrophages (BMDMs) were stimulated with various ligands in the presence or 
      absence of MSC-conditioned medium. For in vivo studies, mice 
      intranasally-inoculated with S. pneumoniae were intravenously treated with MSCs 
      or vehicle, and various parameters were assessed. RESULTS: After stimulation with 
      toll-like receptor (TLR) 2, TLR9 or TLR4 ligands, or live S. pneumoniae, TNF-alpha 
      and interleukin (IL)-6 levels were significantly decreased, whereas IL-10 was 
      significantly increased in BMDMs cultured in MSC-conditioned medium. In mice, MSC 
      treatment decreased the number of neutrophils in bronchoalveolar lavage fluid 
      (BALF) after pneumococcal infection, and this was associated with a decrease in 
      myeloperoxidase activity in the lungs. Levels of proinflammatory cytokines, 
      including TNF-alpha, IL-6, GM-CSF and IFN-gamma, were significantly lower in MSC-treated 
      mice, and the bacterial load in the lung after pneumococcal infection was 
      significantly reduced. In addition, histopathologic analysis confirmed a decrease 
      in the number of cells recruited to the lungs; however, lung edema, protein 
      leakage into the BALF and levels of the antibacterial protein lipocalin 2 in the 
      BALF were comparable between the groups. CONCLUSIONS: These results indicate that 
      MSCs could represent a potential therapeutic application for the treatment of 
      pneumonia caused by S. pneumoniae.
CI  - Copyright (c) 2018 International Society for Cellular Therapy. Published by 
      Elsevier Inc. All rights reserved.
FAU - Asami, Takahiro
AU  - Asami T
AD  - Division of Pulmonary Medicine, Department of Medicine, Keio University School of 
      Medicine, Tokyo, Japan.
FAU - Ishii, Makoto
AU  - Ishii M
AD  - Division of Pulmonary Medicine, Department of Medicine, Keio University School of 
      Medicine, Tokyo, Japan. Electronic address: ishii@keio.jp.
FAU - Namkoong, Ho
AU  - Namkoong H
AD  - Division of Pulmonary Medicine, Department of Medicine, Keio University School of 
      Medicine, Tokyo, Japan.
FAU - Yagi, Kazuma
AU  - Yagi K
AD  - Division of Pulmonary Medicine, Department of Medicine, Keio University School of 
      Medicine, Tokyo, Japan.
FAU - Tasaka, Sadatomo
AU  - Tasaka S
AD  - Department of Respiratory Medicine, Hirosaki University Graduate School of 
      Medicine, Hirosaki, Japan.
FAU - Asakura, Takanori
AU  - Asakura T
AD  - Division of Pulmonary Medicine, Department of Medicine, Keio University School of 
      Medicine, Tokyo, Japan.
FAU - Suzuki, Shoji
AU  - Suzuki S
AD  - Division of Pulmonary Medicine, Department of Medicine, Keio University School of 
      Medicine, Tokyo, Japan.
FAU - Kamo, Tetsuro
AU  - Kamo T
AD  - Division of Pulmonary Medicine, Department of Medicine, Keio University School of 
      Medicine, Tokyo, Japan.
FAU - Okamori, Satoshi
AU  - Okamori S
AD  - Division of Pulmonary Medicine, Department of Medicine, Keio University School of 
      Medicine, Tokyo, Japan.
FAU - Kamata, Hirofumi
AU  - Kamata H
AD  - Division of Pulmonary Medicine, Department of Medicine, Keio University School of 
      Medicine, Tokyo, Japan.
FAU - Zhang, Haiyue
AU  - Zhang H
AD  - Division of Pulmonary Medicine, Department of Medicine, Keio University School of 
      Medicine, Tokyo, Japan.
FAU - Hegab, Ahmed E
AU  - Hegab AE
AD  - Division of Pulmonary Medicine, Department of Medicine, Keio University School of 
      Medicine, Tokyo, Japan.
FAU - Hasegawa, Naoki
AU  - Hasegawa N
AD  - Center for Infectious Disease and Infection Control, Keio University School of 
      Medicine, Tokyo, Japan.
FAU - Betsuyaku, Tomoko
AU  - Betsuyaku T
AD  - Division of Pulmonary Medicine, Department of Medicine, Keio University School of 
      Medicine, Tokyo, Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180212
PL  - England
TA  - Cytotherapy
JT  - Cytotherapy
JID - 100895309
RN  - 0 (Culture Media, Conditioned)
RN  - 0 (Cytokines)
RN  - 0 (Ligands)
RN  - 0 (Toll-Like Receptors)
SB  - IM
MH  - Animals
MH  - Culture Media, Conditioned/metabolism/pharmacology
MH  - Cytokines/metabolism
MH  - Ligands
MH  - Lung/metabolism/microbiology/pathology
MH  - Macrophages/immunology/metabolism
MH  - Male
MH  - Mesenchymal Stem Cell Transplantation/*methods
MH  - Mesenchymal Stem Cells/*immunology
MH  - Mice, Inbred C57BL
MH  - Neutrophils/immunology
MH  - Pneumonia, Pneumococcal/immunology/*therapy
MH  - Streptococcus pneumoniae/pathogenicity
MH  - Toll-Like Receptors/immunology
OTO - NOTNLM
OT  - Streptococcus pneumoniae
OT  - cell therapy
OT  - mesenchymal stromal cells
OT  - pneumonia
EDAT- 2018/02/06 06:00
MHDA- 2019/05/21 06:00
CRDT- 2018/02/05 06:00
PHST- 2017/05/22 00:00 [received]
PHST- 2017/12/30 00:00 [revised]
PHST- 2018/01/02 00:00 [accepted]
PHST- 2018/02/06 06:00 [pubmed]
PHST- 2019/05/21 06:00 [medline]
PHST- 2018/02/05 06:00 [entrez]
AID - S1465-3249(18)30009-4 [pii]
AID - 10.1016/j.jcyt.2018.01.003 [doi]
PST - ppublish
SO  - Cytotherapy. 2018 Mar;20(3):302-313. doi: 10.1016/j.jcyt.2018.01.003. Epub 2018 
      Feb 12.