PMID- 25573338
OWN - NLM
STAT- MEDLINE
DCOM- 20151005
LR  - 20230728
IS  - 1791-244X (Electronic)
IS  - 1107-3756 (Print)
IS  - 1107-3756 (Linking)
VI  - 35
IP  - 3
DP  - 2015 Mar
TI  - Chronic alcohol exposure exacerbates inflammation and triggers pancreatic 
      acinar-to-ductal metaplasia through PI3K/Akt/IKK.
PG  - 653-63
LID - 10.3892/ijmm.2014.2055 [doi]
AB  - Pancreatic acinar-to-ductal metaplasia (ADM) has been identified as an initiating 
      event that can progress to pancreatic intraepithelial neoplasia (PanIN) or 
      pancreatic ductal adenocarcinoma (PDAC). Acini transdifferentiation can be 
      induced by persistent inflammation. Notably, compelling evidence has emerged that 
      chronic alcohol exposure may trigger an inflammatory response of 
      macrophages/monocytes stimulated by endotoxins. In the present study, we aimed to 
      evaluate the role of inflammation induced by chronic alcohol and 
      lipopolysaccharide (LPS) exposure in the progression of pancreatic ADM, as well 
      as to elucidate the possible mechanisms involved. For this purpose, cultured 
      macrophages were exposed to varying doses of alcohol for 1 week prior to 
      stimulation with LPS. Tumor necrosis factor-alpha (TNF-alpha) and regulated upon 
      activation, normal T cell expression and secreted (RANTES) expression were 
      upregulated in the intoxicated macrophages with activated nuclear factor-kappaB 
      (NF-kappaB). Following treatment with the supernatant of intoxicated macrophages, ADM 
      of primary acinar cells was induced. Furthermore, the expression of TNF-alpha and 
      RANTES, as well as the phosphatidylinositol-3-kinase (PI3K)/protein kinase 
      B(Akt)/inhibitory kappaB kinase (IKK) signaling pathway have been proven to be 
      involved in the ADM of acinar cells. Moreover, Sprague-Dawley (SD) rats were 
      employed to further explore the induction of pancreatic ADM by chronic alcohol 
      and LPS exposure in vivo. At the end of the treatment period, a number of 
      physiological parameters, such as body weight, liver weight and pancreatic weight 
      were reduced in the exposed rats. Plasma alcohol concentrations and oxidative 
      stress levels in the serum, as well as TNF-alpha and RANTES expression in monocytes 
      were also induced following chronic alcohol and LPS exposure. In addition, 
      pancreatic ADM was induced through the PI3K/Akt/IKK signaling pathway by the 
      augmented TNF-alpha and RANTES expression levels in the exposed rats. Overall, we 
      characterized the link between inflammation induced by chronic alcohol and LPS 
      exposure and pancreatic ADM. However, the mechanisms behind the induction of 
      pancreatic ADM warrant further investigation.
FAU - Huang, Xin
AU  - Huang X
AD  - Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi'an Jiaotong 
      University, Xi'an 710061, P.R. China.
FAU - Li, Xuqi
AU  - Li X
AD  - Department of General Surgery, First Affiliated Hospital of Xi'an Jiaotong 
      University, Xi'an 710061, P.R. China.
FAU - Ma, Qingyong
AU  - Ma Q
AD  - Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi'an Jiaotong 
      University, Xi'an 710061, P.R. China.
FAU - Xu, Qinhong
AU  - Xu Q
AD  - Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi'an Jiaotong 
      University, Xi'an 710061, P.R. China.
FAU - Duan, Wanxing
AU  - Duan W
AD  - Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi'an Jiaotong 
      University, Xi'an 710061, P.R. China.
FAU - Lei, Jianjun
AU  - Lei J
AD  - Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi'an Jiaotong 
      University, Xi'an 710061, P.R. China.
FAU - Zhang, Lun
AU  - Zhang L
AD  - Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi'an Jiaotong 
      University, Xi'an 710061, P.R. China.
FAU - Wu, Zheng
AU  - Wu Z
AD  - Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi'an Jiaotong 
      University, Xi'an 710061, P.R. China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Retracted Publication
DEP - 20141229
PL  - Greece
TA  - Int J Mol Med
JT  - International journal of molecular medicine
JID - 9810955
RN  - 0 (Alcohols)
RN  - 0 (Chemokine CCL5)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (NF-kappa B)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
SB  - IM
RIN - Int J Mol Med. 2023 Sep;52(3):. PMID: 37503753
MH  - Alcohols/*administration & dosage
MH  - Animals
MH  - Carcinoma, Pancreatic Ductal/*etiology/*metabolism/*pathology
MH  - Chemokine CCL5/genetics/metabolism
MH  - Enzyme Activation
MH  - Gene Expression
MH  - Gene Knockdown Techniques
MH  - Inflammation/*metabolism/*pathology
MH  - Lipopolysaccharides
MH  - MAP Kinase Signaling System
MH  - Macrophages/metabolism
MH  - Male
MH  - Metaplasia/*metabolism
MH  - Monocytes/metabolism
MH  - NF-kappa B/genetics
MH  - Phosphatidylinositol 3-Kinases
MH  - Proto-Oncogene Proteins c-akt/*metabolism
MH  - Rats
MH  - Tumor Necrosis Factor-alpha/metabolism
PMC - PMC4314411
EDAT- 2015/01/13 06:00
MHDA- 2015/10/06 06:00
PMCR- 2014/12/29
CRDT- 2015/01/10 06:00
PHST- 2014/05/02 00:00 [received]
PHST- 2014/11/20 00:00 [accepted]
PHST- 2015/01/10 06:00 [entrez]
PHST- 2015/01/13 06:00 [pubmed]
PHST- 2015/10/06 06:00 [medline]
PHST- 2014/12/29 00:00 [pmc-release]
AID - ijmm-35-03-0653 [pii]
AID - 10.3892/ijmm.2014.2055 [doi]
PST - ppublish
SO  - Int J Mol Med. 2015 Mar;35(3):653-63. doi: 10.3892/ijmm.2014.2055. Epub 2014 Dec 
      29.