PMID- 28237874
OWN - NLM
STAT- MEDLINE
DCOM- 20180226
LR  - 20181113
IS  - 1096-0023 (Electronic)
IS  - 1043-4666 (Print)
IS  - 1043-4666 (Linking)
VI  - 95
DP  - 2017 Jul
TI  - Interleukin-37 suppresses the inflammatory response to protect cardiac function 
      in old endotoxemic mice.
PG  - 55-63
LID - S1043-4666(17)30045-5 [pii]
LID - 10.1016/j.cyto.2017.02.008 [doi]
AB  - Myocardial inflammatory responses to endotoxemia are enhanced in old mice, which 
      results in worse cardiac dysfunction. Anti-inflammatory cytokine interleukin 
      (IL)-37 has a broad effect on innate immunoresponses. We hypothesized that IL-37 
      suppresses myocardial inflammatory responses to protect cardiac function during 
      endotoxemia in old mice. Old (20-24month) wild-type (WT), and IL-37 transgenic 
      (IL-37tg) mice were treated with lipopolysaccharide (LPS, 0.5mg/kg, iv) or normal 
      saline (0.1ml/mouse, iv). Six hours later, left ventricle (LV) function was 
      assessed using a pressure-volume microcatheter. Levels of monocyte 
      chemoattractant protein-1 (MCP-1), tumor necrosis factor-alpha (TNF-alpha), interleukin 
      (IL)-1beta and IL-6 in plasma and myocardial tissue, as well as mononuclear cell 
      density in the myocardium, were examined. Cardiac microvascular endothelial cells 
      isolated from WT and IL-37tg mice were treated with LPS (0.2microg/ml) for 0.5-24h. 
      Nuclear factor-kappa B (NF-kappaB) p65 phosphorylation was examined by 
      immunoblotting, and MCP-1 levels in cell culture supernatant was determined using 
      enzyme-linked immunosorbent assay. LV dysfunction in old WT endotoxemic mice was 
      accompanied by up-regulated MCP-1, myocardial accumulation of mononuclear cells 
      and production of TNF-alpha, IL-1beta and IL-6. Expression of IL-37 suppressed 
      myocardial inflammatory responses to endotoxemia in old mice, resulting in 
      improved LV function. Treatment of old WT endotoxemic mice with recombinant IL-37 
      also improved LV function. In vitro experiments revealed that cardiac 
      microvascular endothelial cells from IL-37tg mice had attenuated NF-kappaB activation 
      and MCP-1 production following LPS stimulation. In conclusion, IL-37 is potent to 
      suppress myocardial inflammation and protects against cardiac dysfunction during 
      endotoxemia in old mice.
CI  - Copyright (c) 2017 Elsevier Ltd. All rights reserved.
FAU - Li, Jilin
AU  - Li J
AD  - Departments of Surgery, University of Colorado Denver, Aurora, CO 80045, USA; 
      Division of Cardiology, the First Affiliated Hospital, Shantou University Medical 
      College, Shantou 515041, China.
FAU - Zhai, Yufeng
AU  - Zhai Y
AD  - Departments of Surgery, University of Colorado Denver, Aurora, CO 80045, USA.
FAU - Ao, Lihua
AU  - Ao L
AD  - Departments of Surgery, University of Colorado Denver, Aurora, CO 80045, USA.
FAU - Hui, Haipeng
AU  - Hui H
AD  - Departments of Surgery, University of Colorado Denver, Aurora, CO 80045, USA.
FAU - Fullerton, David A
AU  - Fullerton DA
AD  - Departments of Surgery, University of Colorado Denver, Aurora, CO 80045, USA.
FAU - Dinarello, Charles A
AU  - Dinarello CA
AD  - Departments of Medicine, University of Colorado Denver, Aurora, CO 80045, USA.
FAU - Meng, Xianzhong
AU  - Meng X
AD  - Departments of Surgery, University of Colorado Denver, Aurora, CO 80045, USA; 
      Division of Cardiology, the First Affiliated Hospital, Shantou University Medical 
      College, Shantou 515041, China. Electronic address: Xianzhong.meng@ucdenver.edu.
LA  - eng
GR  - R01 AG039545/AG/NIA NIH HHS/United States
PT  - Journal Article
DEP - 20170224
PL  - England
TA  - Cytokine
JT  - Cytokine
JID - 9005353
RN  - 0 (Ccl2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Cytokines)
RN  - 0 (IL37 protein, human)
RN  - 0 (Interleukin-1)
RN  - 0 (NF-kappa B)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Tlr4 protein, mouse)
RN  - 0 (Toll-Like Receptor 4)
RN  - 126547-89-5 (Intercellular Adhesion Molecule-1)
SB  - IM
MH  - Aging/*physiology
MH  - Animals
MH  - Cells, Cultured
MH  - Chemokine CCL2/metabolism
MH  - Cytokines/metabolism
MH  - Endothelium, Vascular/metabolism
MH  - Endotoxemia/metabolism/pathology/*physiopathology
MH  - Intercellular Adhesion Molecule-1/metabolism
MH  - Interleukin-1/genetics/*physiology
MH  - Male
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Myocardium/cytology/metabolism
MH  - NF-kappa B/metabolism
MH  - Recombinant Proteins/pharmacology
MH  - Toll-Like Receptor 4/metabolism
MH  - *Ventricular Function, Left
PMC - PMC5441934
MID - NIHMS855325
OTO - NOTNLM
OT  - Aging
OT  - Cardiac function
OT  - Cardiac microvascular endothelial cells
OT  - Endotoxemia
OT  - IL-37
COIS- Disclosures The authors declare that they have no competing interests.
EDAT- 2017/02/27 06:00
MHDA- 2018/02/27 06:00
PMCR- 2018/07/01
CRDT- 2017/02/27 06:00
PHST- 2016/09/14 00:00 [received]
PHST- 2017/02/07 00:00 [revised]
PHST- 2017/02/10 00:00 [accepted]
PHST- 2017/02/27 06:00 [pubmed]
PHST- 2018/02/27 06:00 [medline]
PHST- 2017/02/27 06:00 [entrez]
PHST- 2018/07/01 00:00 [pmc-release]
AID - S1043-4666(17)30045-5 [pii]
AID - 10.1016/j.cyto.2017.02.008 [doi]
PST - ppublish
SO  - Cytokine. 2017 Jul;95:55-63. doi: 10.1016/j.cyto.2017.02.008. Epub 2017 Feb 24.