PMID- 23897411
OWN - NLM
STAT- MEDLINE
DCOM- 20131104
LR  - 20230216
IS  - 1530-0307 (Electronic)
IS  - 0023-6837 (Linking)
VI  - 93
IP  - 9
DP  - 2013 Sep
TI  - Protective role of tumor necrosis factor (TNF) receptors in chronic intestinal 
      inflammation: TNFR1 ablation boosts systemic inflammatory response.
PG  - 1024-35
LID - 10.1038/labinvest.2013.89 [doi]
AB  - Tumor necrosis factor-alpha (TNF-alpha) acts as a key factor for the development of 
      inflammatory bowel diseases (IBDs), whose function is known to be mediated by TNF 
      receptor 1 (TNFR1) or TNFR2. However, the precise role of the two receptors in 
      IBD remains poorly understood. Herein, chronic colitis was established by oral 
      administration of dextran sulfate sodium (DSS) in TNFR1 or TNFR2-/- mice. 
      Unexpectedly, TNFR1 or TNFR2 deficiency led to exacerbation of signs of colitis 
      compared with wild-type (WT) counterparts. Of note, TNFR1 ablation rendered 
      significantly increased mortality compared with TNFR2 and WT mice after DSS. 
      Aggravated pathology of colitis in TNFR1-/- or TNFR2-/- mice correlated with 
      elevated colonic expression of proinflammatory cytokines and chemokines. 
      Importantly, ablation of TNFR1 or TNFR2 increased apoptosis of colonic epithelial 
      cells, which might be due to the heightened ratio of Bax/Bcl-2 and increased 
      expression of caspase-8. Intriguingly, despite comparable intensity of intestinal 
      inflammation in TNFR-deficient mice after DSS, systemic inflammatory response 
      (including splenomegaly and myeloid expansion) was augmented dramatically in 
      TNFR1-/- mice, instead of TNFR2-/- mice. Granulocyte-macrophage 
      colony-stimulating factor (GMCSF) was identified as a key mediator in this 
      process, as neutralization of GMCSF dampened peripheral inflammatory reaction and 
      reduced mortality in TNFR1-/- mice. These data suggest that signaling via TNFR1 
      or TNFR2 has a protective role in chronic intestinal inflammation, and that 
      lacking TNFR1 augments systemic inflammatory response in GMCSF-dependent manner.
FAU - Wang, Yi
AU  - Wang Y
AD  - Department of Immunology, Institute of Basic Medical Sciences, Beijing, China.
FAU - Han, Gencheng
AU  - Han G
FAU - Chen, Yu
AU  - Chen Y
FAU - Wang, Ke
AU  - Wang K
FAU - Liu, Guijun
AU  - Liu G
FAU - Wang, Renxi
AU  - Wang R
FAU - Xiao, He
AU  - Xiao H
FAU - Li, Xinying
AU  - Li X
FAU - Hou, Chunmei
AU  - Hou C
FAU - Shen, Beifen
AU  - Shen B
FAU - Guo, Renfeng
AU  - Guo R
FAU - Li, Yan
AU  - Li Y
FAU - Chen, Guojiang
AU  - Chen G
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130729
PL  - United States
TA  - Lab Invest
JT  - Laboratory investigation; a journal of technical methods and pathology
JID - 0376617
RN  - 0 (Receptors, Tumor Necrosis Factor)
RN  - 0 (Receptors, Tumor Necrosis Factor, Type I)
RN  - 0 (Receptors, Tumor Necrosis Factor, Type II)
RN  - 83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor)
RN  - 9042-14-2 (Dextran Sulfate)
SB  - IM
MH  - Animals
MH  - Apoptosis
MH  - Chronic Disease
MH  - Colitis/chemically induced/immunology/*metabolism
MH  - Dextran Sulfate/administration & dosage
MH  - Granulocyte-Macrophage Colony-Stimulating Factor/metabolism
MH  - Histocytochemistry
MH  - Inflammation/immunology/*metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Knockout
MH  - Receptors, Tumor Necrosis Factor
MH  - Receptors, Tumor Necrosis Factor, Type I/genetics/immunology/*metabolism
MH  - Receptors, Tumor Necrosis Factor, Type II/genetics/immunology/*metabolism
EDAT- 2013/07/31 06:00
MHDA- 2013/11/05 06:00
CRDT- 2013/07/31 06:00
PHST- 2013/03/22 00:00 [received]
PHST- 2013/06/13 00:00 [revised]
PHST- 2013/06/18 00:00 [accepted]
PHST- 2013/07/31 06:00 [entrez]
PHST- 2013/07/31 06:00 [pubmed]
PHST- 2013/11/05 06:00 [medline]
AID - S0023-6837(22)00904-7 [pii]
AID - 10.1038/labinvest.2013.89 [doi]
PST - ppublish
SO  - Lab Invest. 2013 Sep;93(9):1024-35. doi: 10.1038/labinvest.2013.89. Epub 2013 Jul 
      29.