PMID- 28733636
OWN - NLM
STAT- MEDLINE
DCOM- 20190225
LR  - 20190225
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 7
IP  - 1
DP  - 2017 Jul 21
TI  - PI3K p85alpha Subunit-deficient Macrophages Protect Mice from Acute Colitis due to 
      the Enhancement of IL-10 Production.
PG  - 6187
LID - 10.1038/s41598-017-06464-w [doi]
LID - 6187
AB  - We investigated the role of the PI3K p85alpha subunit in the development of acute 
      colitis with a focus on intestinal macrophages. Experimental acute colitis was 
      induced using 3% dextran sulfate sodium (DSS) in drinking water for 7 days. The 
      severity of DSS-induced acute colitis was significantly attenuated in p85alpha 
      hetero-deficient (p85alpha+/-) mice compared with WT mice. The expression of 
      proinflammatory mediators in intestinal macrophages isolated from the inflamed 
      colonic mucosa was significantly suppressed in p85alpha+/- colitis mice compared with 
      WT colitis mice. Interestingly, we found that bone marrow-derived macrophages 
      (BMDMs) from p85alpha+/- mice produced a significantly higher amount of IL-10 than 
      BMDMs from WT mice. The adoptive transfer of p85alpha+/- BMDMs, but not WT BMDMs, 
      significantly improved the severity in WT colitis mice, and this effect was 
      reversed by anti-IL-10 antibody. Furthermore, the expression of IL-10 in the 
      intestinal macrophages of p85alpha+/- normal colonic mucosa was significantly higher 
      than that in the intestinal macrophages of WT normal colonic mucosa. The present 
      results demonstrate that p85alpha+/- mice exhibit a reduced susceptibility to 
      DSS-induced acute colitis. Our study suggests that a deficiency of PI3K p85alpha 
      enhances the production of IL-10 in intestinal macrophages, thereby suppressing 
      the development of DSS-induced acute colitis.
FAU - Hayashi, Shusaku
AU  - Hayashi S
AD  - Division of Gastrointestinal Pathophysiology, Institute of Natural Medicine, 
      University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan. 
      hayashi@inm.u-toyama.ac.jp.
FAU - Hamada, Takayuki
AU  - Hamada T
AD  - Division of Gastrointestinal Pathophysiology, Institute of Natural Medicine, 
      University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan.
FAU - Zinsou, Donald G A
AU  - Zinsou DGA
AD  - Division of Gastrointestinal Pathophysiology, Institute of Natural Medicine, 
      University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan.
FAU - Oshiro, Momoe
AU  - Oshiro M
AD  - Division of Gastrointestinal Pathophysiology, Institute of Natural Medicine, 
      University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan.
FAU - Itoi, Kana
AU  - Itoi K
AD  - Division of Gastrointestinal Pathophysiology, Institute of Natural Medicine, 
      University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan.
FAU - Yamamoto, Takeshi
AU  - Yamamoto T
AD  - Division of Gastrointestinal Pathophysiology, Institute of Natural Medicine, 
      University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan.
FAU - Kadowaki, Makoto
AU  - Kadowaki M
AD  - Division of Gastrointestinal Pathophysiology, Institute of Natural Medicine, 
      University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20170721
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (IL10 protein, mouse)
RN  - 130068-27-8 (Interleukin-10)
RN  - 9042-14-2 (Dextran Sulfate)
RN  - EC 2.7.1.137 (Class Ia Phosphatidylinositol 3-Kinase)
RN  - EC 2.7.1.137 (Pik3r1 protein, mouse)
SB  - IM
MH  - Adoptive Transfer
MH  - Animals
MH  - Class Ia Phosphatidylinositol 3-Kinase/*deficiency
MH  - Colitis/chemically induced/*drug therapy/metabolism
MH  - Dextran Sulfate/*adverse effects
MH  - Disease Models, Animal
MH  - Interleukin-10/*metabolism
MH  - Macrophages/metabolism/*transplantation
MH  - Male
MH  - Mice
MH  - Severity of Illness Index
PMC - PMC5522489
COIS- The authors declare that they have no competing interests.
EDAT- 2017/07/25 06:00
MHDA- 2019/02/26 06:00
PMCR- 2017/07/21
CRDT- 2017/07/23 06:00
PHST- 2016/11/07 00:00 [received]
PHST- 2017/06/13 00:00 [accepted]
PHST- 2017/07/23 06:00 [entrez]
PHST- 2017/07/25 06:00 [pubmed]
PHST- 2019/02/26 06:00 [medline]
PHST- 2017/07/21 00:00 [pmc-release]
AID - 10.1038/s41598-017-06464-w [pii]
AID - 6464 [pii]
AID - 10.1038/s41598-017-06464-w [doi]
PST - epublish
SO  - Sci Rep. 2017 Jul 21;7(1):6187. doi: 10.1038/s41598-017-06464-w.