PMID- 31582793
OWN - NLM
STAT- MEDLINE
DCOM- 20201102
LR  - 20210110
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 9
IP  - 1
DP  - 2019 Oct 3
TI  - Stimulator of interferon genes (STING) activation exacerbates experimental 
      colitis in mice.
PG  - 14281
LID - 10.1038/s41598-019-50656-5 [doi]
LID - 14281
AB  - Detection of cytoplasmic DNA by the host's innate immune system is essential for 
      microbial and endogenous pathogen recognition. In mammalian cells, an important 
      sensor is the stimulator of interferon genes (STING) protein, which upon 
      activation by bacterially-derived cyclic dinucleotides (cDNs) or cytosolic dsDNA 
      (dsDNA), triggers type I interferons and pro-inflammatory cytokine production. 
      Given the abundance of bacterially-derived cDNs in the gut, we determined whether 
      STING deletion, or stimulation, acts to modulate the severity of intestinal 
      inflammation in the dextran sodium sulphate (DSS) model of colitis. DSS was 
      administered to Tmem173(gt) (STING-mutant) mice and to wild-type mice co-treated 
      with DSS and a STING agonist. Colitis severity was markedly reduced in the 
      DSS-treated Tmem173(gt) mice and greatly exacerbated in wild-type mice co-treated 
      with the STING agonist. STING expression levels were also assessed in colonic 
      tissues, murine bone marrow derived macrophages (BMDMs), and human THP-1 cells. 
      M1 and M2 polarized THP-1 and murine BMDMs were also stimulated with STING 
      agonists and ligands to assess their responses. STING expression was increased in 
      both murine and human M1 polarized macrophages and a STING agonist repolarized M2 
      macrophages towards an M1-like subtype. Our results suggest that STING is 
      involved in the host's response to acutely-induced colitis.
FAU - Martin, Gary R
AU  - Martin GR
AD  - Department of Biochemistry & Molecular Biology and The McCaig Institute for Bone 
      & Joint Health, University of Calgary, Calgary, Alberta, Canada. 
      marting@ucalgary.ca.
FAU - Blomquist, Charlene M
AU  - Blomquist CM
AD  - Department of Biochemistry & Molecular Biology and The McCaig Institute for Bone 
      & Joint Health, University of Calgary, Calgary, Alberta, Canada.
FAU - Henare, Kimiora L
AU  - Henare KL
AUID- ORCID: 0000-0001-5113-0700
AD  - Department of Biochemistry & Molecular Biology and The McCaig Institute for Bone 
      & Joint Health, University of Calgary, Calgary, Alberta, Canada.
AD  - Auckland Cancer Society Research Centre, The University of Auckland, Auckland, 
      New Zealand.
FAU - Jirik, Frank R
AU  - Jirik FR
AD  - Department of Biochemistry & Molecular Biology and The McCaig Institute for Bone 
      & Joint Health, University of Calgary, Calgary, Alberta, Canada. 
      jirik@ucalgary.ca.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20191003
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Membrane Proteins)
RN  - 0 (Sting1 protein, mouse)
RN  - 9042-14-2 (Dextran Sulfate)
SB  - IM
MH  - Animals
MH  - Cells, Cultured
MH  - Colitis/chemically induced/genetics/immunology/*pathology
MH  - Dextran Sulfate
MH  - Disease Models, Animal
MH  - Gene Deletion
MH  - Immunity, Innate
MH  - Inflammation/genetics/immunology/*pathology
MH  - Macrophage Activation
MH  - Male
MH  - Membrane Proteins/analysis/genetics/*immunology
MH  - Mice
MH  - Mice, Inbred C57BL
PMC - PMC6776661
COIS- The authors declare no competing interests.
EDAT- 2019/10/05 06:00
MHDA- 2020/11/03 06:00
PMCR- 2019/10/03
CRDT- 2019/10/05 06:00
PHST- 2019/04/03 00:00 [received]
PHST- 2019/09/16 00:00 [accepted]
PHST- 2019/10/05 06:00 [entrez]
PHST- 2019/10/05 06:00 [pubmed]
PHST- 2020/11/03 06:00 [medline]
PHST- 2019/10/03 00:00 [pmc-release]
AID - 10.1038/s41598-019-50656-5 [pii]
AID - 50656 [pii]
AID - 10.1038/s41598-019-50656-5 [doi]
PST - epublish
SO  - Sci Rep. 2019 Oct 3;9(1):14281. doi: 10.1038/s41598-019-50656-5.