PMID- 15596091
OWN - NLM
STAT- MEDLINE
DCOM- 20050524
LR  - 20131121
IS  - 0741-8329 (Print)
IS  - 0741-8329 (Linking)
VI  - 33
IP  - 3
DP  - 2004 Jul
TI  - Stabilization of tumor necrosis factor-alpha mRNA in macrophages in response to 
      chronic ethanol exposure.
PG  - 229-33
AB  - Tumor necrosis factor-alpha (TNF-alpha) is one of a number of cytokines 
      implicated in the progression of alcohol-induced liver disease. Activation of 
      hepatic macrophages by lipopolysaccharide (LPS) during exposure to ethanol is 
      thought to be an important mechanism for stimulation of TNF-alpha expression. 
      Chronic exposure of macrophages to ethanol, both in vivo after ad libitum feeding 
      of ethanol for 4 weeks and in culture for 48 h, has an impact on specific 
      elements within the LPS-stimulated signaling cascade, disrupting both 
      transcriptional and posttranscriptional regulation of TNF-alpha biosynthesis. 
      Stabilization of TNF-alpha mRNA after chronic exposure to ethanol is one 
      important mechanism for increased TNF-alpha production by hepatic macrophages. 
      Increased LPS stimulation of p38 mitogen-activated protein kinase contributes to 
      this stabilization of TNF-alpha mRNA in macrophages. Stabilization of TNF-alpha 
      mRNA after chronic exposure to ethanol requires both cis-acting elements in the 
      TNF-alpha mRNA and trans-acting mRNA-binding proteins. The adenosine plus 
      uridine-rich element in the 3' untranslated region of the TNF-alpha mRNA is an 
      important regulator of TNF-alpha mRNA stability. Its activity is required for 
      stabilization of TNF-alpha mRNA induced by chronic exposure to ethanol. Moreover, 
      results from studies have demonstrated that at least one mRNA-binding protein, 
      HuR, is also involved in stabilization of TNF-alpha mRNA stability after chronic 
      exposure to ethanol. Taken together, the results from these studies identify the 
      regulation of TNF-alpha mRNA stability as a novel mechanism by which chronic 
      exposure to ethanol increases the expression of TNF-alpha.
FAU - Nagy, Laura E
AU  - Nagy LE
AD  - Department of Nutrition, Case Western Reserve University, 2123 Abington Road, 
      Room 201, Cleveland, OH 44106-4906, USA. len2@po.cwru.edu
LA  - eng
GR  - AA 11975/AA/NIAAA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PT  - Review
PL  - United States
TA  - Alcohol
JT  - Alcohol (Fayetteville, N.Y.)
JID - 8502311
RN  - 0 (RNA, Messenger)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 3K9958V90M (Ethanol)
SB  - IM
MH  - Animals
MH  - Ethanol/*administration & dosage
MH  - Humans
MH  - Macrophages/*drug effects/immunology/metabolism
MH  - RNA, Messenger/*biosynthesis/immunology
MH  - Tumor Necrosis Factor-alpha/*biosynthesis/immunology
RF  - 75
EDAT- 2004/12/15 09:00
MHDA- 2005/05/25 09:00
CRDT- 2004/12/15 09:00
PHST- 2004/03/09 00:00 [received]
PHST- 2004/06/23 00:00 [revised]
PHST- 2004/06/29 00:00 [accepted]
PHST- 2004/12/15 09:00 [pubmed]
PHST- 2005/05/25 09:00 [medline]
PHST- 2004/12/15 09:00 [entrez]
AID - S0741-8329(04)00105-3 [pii]
AID - 10.1016/j.alcohol.2004.09.002 [doi]
PST - ppublish
SO  - Alcohol. 2004 Jul;33(3):229-33. doi: 10.1016/j.alcohol.2004.09.002.