PMID- 24237301
OWN - NLM
STAT- MEDLINE
DCOM- 20141118
LR  - 20220330
IS  - 1557-7465 (Electronic)
IS  - 1079-9907 (Linking)
VI  - 34
IP  - 3
DP  - 2014 Mar
TI  - Interferon-gamma-induced intestinal epithelial barrier dysfunction by NF-kappaB/HIF-1alpha 
      pathway.
PG  - 195-203
LID - 10.1089/jir.2013.0044 [doi]
AB  - Interferon-gamma (IFN-gamma) plays an important role in intestinal barrier dysfunction. 
      However, the mechanisms are not fully understood. As hypoxia-inducible factor-1 
      (HIF-1) is a critical determinant response to hypoxia and inflammation, which has 
      been shown to be deleterious to intestinal barrier function, we hypothesized that 
      IFN-gamma induces loss of barrier function through the regulation of HIF-1alpha 
      activation and function. In this study, we detected the expressions of HIF-1alpha and 
      tight junction proteins in IFN-gamma-treated T84 intestinal epithelial cell line. 
      IFN-gamma led to an increase of HIF-1alpha expression in time- and dose-dependent manners 
      but did not change the expression of HIF-1beta. The IFN-gamma-induced increase in HIF-1alpha 
      was associated with an activation of NF-kappaB. Treatment with the NF-kappaB inhibitor, 
      pyrolidinedithiocarbamate (PDTC), significantly suppressed the activation of 
      NF-kappaB and the expression of HIF-1alpha. In addition, IFN-gamma also increased intestinal 
      epithelial permeability and depletion of tight junction proteins; inhibition of 
      NF-kappaB or HIF-1alpha prevented the increase in intestinal permeability and alteration 
      in tight junction protein expressions. Interestingly, we demonstrated that a 
      significant portion of IFN-gamma activation NF-kB and modulation tight junction 
      expression is mediated through HIF-1alpha. Taken together, this study suggested that 
      IFN-gamma induced the loss of epithelial barrier function and disruption of tight 
      junction proteins, by upregulation of HIF-1alpha expression through NF-kappaB pathway.
FAU - Yang, Songwei
AU  - Yang S
AD  - 1 Department of General Surgery, Xinqiao Hospital, Third Military Medical 
      University , Chongqing, China .
FAU - Yu, Min
AU  - Yu M
FAU - Sun, Lihua
AU  - Sun L
FAU - Xiao, Weidong
AU  - Xiao W
FAU - Yang, Xuechao
AU  - Yang X
FAU - Sun, Ligang
AU  - Sun L
FAU - Zhang, Chaojun
AU  - Zhang C
FAU - Ma, Yuanhang
AU  - Ma Y
FAU - Yang, Hanwenbo
AU  - Yang H
FAU - Liu, Yong
AU  - Liu Y
FAU - Lu, Dingsong
AU  - Lu D
FAU - Teitelbaum, Daniel H
AU  - Teitelbaum DH
FAU - Yang, Hua
AU  - Yang H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20131115
PL  - United States
TA  - J Interferon Cytokine Res
JT  - Journal of interferon & cytokine research : the official journal of the 
      International Society for Interferon and Cytokine Research
JID - 9507088
RN  - 0 (Antineoplastic Agents)
RN  - 0 (HIF1A protein, human)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Thiocarbamates)
RN  - 0 (Tight Junction Proteins)
RN  - 0 (Transcription Factor RelA)
RN  - 135467-92-4 (prolinedithiocarbamate)
RN  - 138391-32-9 (Aryl Hydrocarbon Receptor Nuclear Translocator)
RN  - 82115-62-6 (Interferon-gamma)
RN  - 9DLQ4CIU6V (Proline)
RN  - EC 2.7.11.10 (I-kappa B Kinase)
SB  - IM
MH  - Antineoplastic Agents/pharmacology
MH  - Aryl Hydrocarbon Receptor Nuclear Translocator/biosynthesis
MH  - Cell Line
MH  - Electric Impedance
MH  - Enzyme Activation/immunology
MH  - Epithelial Cells/immunology
MH  - Humans
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/antagonists & 
      inhibitors/biosynthesis/*immunology
MH  - I-kappa B Kinase/immunology
MH  - Inflammation/immunology
MH  - Interferon-gamma/*pharmacology
MH  - Intestinal Mucosa/*pathology
MH  - Proline/analogs & derivatives/pharmacology
MH  - Signal Transduction
MH  - Thiocarbamates/pharmacology
MH  - Tight Junction Proteins/immunology
MH  - Tight Junctions/*pathology
MH  - Transcription Factor RelA/antagonists & inhibitors/*immunology
EDAT- 2013/11/19 06:00
MHDA- 2014/11/19 06:00
CRDT- 2013/11/19 06:00
PHST- 2013/11/19 06:00 [entrez]
PHST- 2013/11/19 06:00 [pubmed]
PHST- 2014/11/19 06:00 [medline]
AID - 10.1089/jir.2013.0044 [doi]
PST - ppublish
SO  - J Interferon Cytokine Res. 2014 Mar;34(3):195-203. doi: 10.1089/jir.2013.0044. 
      Epub 2013 Nov 15.