PMID- 15653932
OWN - NLM
STAT- MEDLINE
DCOM- 20050428
LR  - 20180815
IS  - 1044-1549 (Print)
IS  - 1044-1549 (Linking)
VI  - 32
IP  - 4
DP  - 2005 Apr
TI  - Tumor necrosis factor-alpha induces transforming growth factor-beta1 expression 
      in lung fibroblasts through the extracellular signal-regulated kinase pathway.
PG  - 342-9
AB  - Increased expression of transforming growth factor (TGF)-beta(1) and tumor 
      necrosis factor (TNF)-alpha are thought to play important roles in the 
      development of pulmonary fibrosis. We recently reported that TNF-alpha 
      upregulates TGF-beta(1) expression in primary mouse lung fibroblasts (MLFs), a 
      key cell population in fibrogenesis. In the present study, we have investigated 
      signal transduction pathways involved in TNF-alpha upregulation of TGF-beta(1) in 
      both primary MLFs and the Swiss 3T3 fibroblast cell line. Treatment of 
      fibroblasts with TNF-alpha resulted in a significant increase in TGF-beta(1) 
      protein as measured by ELISA. The increase in protein was preceded by a 200-400% 
      increase in TGF-beta(1) mRNA detected by quantitative, real-time, reverse 
      transcriptase-polymerase chain reaction. Western blot analysis showed that 
      TNF-alpha activated the extracellular signal-regulated kinase (ERK), and 
      inhibitors of the ERK-specific mitogen-activated protein kinase pathway (PD98059 
      or U0126) blocked TNF-alpha induction of TGF-beta(1) mRNA and protein. mRNA 
      stability experiments showed that TNF-alpha increased the half-life of 
      TGF-beta(1) mRNA to more than 24 h compared with approximately 15 h in 
      unstimulated cells. Expression of constitutively active MEK1 that selectively 
      phosphorylates ERK was sufficient for TGF-beta(1) mRNA stabilization in Swiss 3T3 
      fibroblasts. These results indicate that TNF-alpha activates the ERK-specific 
      mitogen-activated protein kinase pathway leading to increased TGF-beta(1) 
      production in fibroblasts, primarily via a post-transcriptional mechanism that 
      involves stabilization of the TGF-beta(1) transcript.
FAU - Sullivan, Deborah E
AU  - Sullivan DE
AD  - Department of Pathology and Laboratory Medicine, Lung Biology Program, Tulane 
      University Health Sciences Center, 1430 Tulane Avenue, New Orleans, LA 70112, 
      USA. dsulliva@tulane.edu
FAU - Ferris, MaryBeth
AU  - Ferris M
FAU - Pociask, Derek
AU  - Pociask D
FAU - Brody, Arnold R
AU  - Brody AR
LA  - eng
GR  - ES06766/ES/NIEHS NIH HHS/United States
GR  - HL60532/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20050114
PL  - United States
TA  - Am J Respir Cell Mol Biol
JT  - American journal of respiratory cell and molecular biology
JID - 8917225
RN  - 0 (Butadienes)
RN  - 0 (DNA, Complementary)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Flavonoids)
RN  - 0 (Nitriles)
RN  - 0 (RNA, Messenger)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Tgfb1 protein, mouse)
RN  - 0 (Transforming Growth Factor beta)
RN  - 0 (Transforming Growth Factor beta1)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (U 0126)
RN  - SJE1IO5E3I (2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one)
SB  - IM
MH  - Animals
MH  - Base Sequence
MH  - Butadienes/pharmacology
MH  - Cells, Cultured
MH  - DNA, Complementary/genetics
MH  - Enzyme Inhibitors/pharmacology
MH  - Fibroblasts/drug effects/metabolism
MH  - Flavonoids/pharmacology
MH  - Gene Expression/drug effects
MH  - Lung/*drug effects/*metabolism
MH  - MAP Kinase Signaling System/drug effects
MH  - Mice
MH  - Nitriles/pharmacology
MH  - RNA Stability/drug effects
MH  - RNA, Messenger/genetics/metabolism
MH  - Recombinant Proteins/pharmacology
MH  - Swiss 3T3 Cells
MH  - Transforming Growth Factor beta/*biosynthesis/*genetics
MH  - Transforming Growth Factor beta1
MH  - Tumor Necrosis Factor-alpha/*pharmacology
EDAT- 2005/01/18 09:00
MHDA- 2005/04/29 09:00
CRDT- 2005/01/18 09:00
PHST- 2005/01/18 09:00 [pubmed]
PHST- 2005/04/29 09:00 [medline]
PHST- 2005/01/18 09:00 [entrez]
AID - 2004-0288OC [pii]
AID - 10.1165/rcmb.2004-0288OC [doi]
PST - ppublish
SO  - Am J Respir Cell Mol Biol. 2005 Apr;32(4):342-9. doi: 10.1165/rcmb.2004-0288OC. 
      Epub 2005 Jan 14.