PMID- 12816730
OWN - NLM
STAT- MEDLINE
DCOM- 20040120
LR  - 20131121
IS  - 1044-1549 (Print)
IS  - 1044-1549 (Linking)
VI  - 29
IP  - 6
DP  - 2003 Dec
TI  - Overexpression of tumor necrosis factor-alpha diminishes pulmonary fibrosis 
      induced by bleomycin or transforming growth factor-beta.
PG  - 669-76
AB  - Tumor necrosis factor-alpha (TNF-alpha) is thought to be important in the 
      development of pulmonary fibrosis. However, surfactant protein-C/TNF-alpha 
      transgenic mice do not spontaneously develop pulmonary fibrosis but instead 
      develop alveolar enlargement and loss of elastic recoil. We hypothesized that 
      overexpression of TNF-alpha in the lung requires an additional insult to produce 
      fibrosis. In this study we evaluated whether TNF-alpha overexpression altered the 
      development of pulmonary fibrosis due to bleomycin or transforming growth 
      factor-beta (TGF-beta). Either 0.2 U bleomycin or saline was administered into 
      left lung of TNF-alpha transgenic mice and their transgene-negative littermates. 
      To overexpress TGF-beta, an adenovirus vector containing either active TGF-beta 
      (AdTGF-beta) or LacZ was administered at a dose of 3 x 108 plaque-forming units 
      per mouse. Fibrosis was assessed histologically and by measurement of 
      hydroxyproline. TNF-alpha transgenic mice tolerated bleomycin or AdTGF-beta, 
      whereas the transgene-negative littermates demonstrated severe pulmonary fibrosis 
      after either agent. An increase in prostaglandin E2 and downregulation of TNF 
      receptor I expression were observed in the TNF-alpha transgenic mice. In 
      addition, recombinant human TNF-alpha attenuated bleomycin-induced pulmonary 
      fibrosis. TNF-alpha has a complex role in the development of pulmonary fibrosis. 
      Endogenous TNF-alpha may be important in the development of fibrosis as indicated 
      in other reports, but overexpression of TNF-alpha or exogenous TNF-alpha limits 
      pulmonary fibrosis in mice.
FAU - Fujita, Masaki
AU  - Fujita M
AD  - Department of Medicine, National Jewish Medical and Research Center, 1400 Jackson 
      Street, Denver, CO 80206, USA.
FAU - Shannon, John M
AU  - Shannon JM
FAU - Morikawa, Osamu
AU  - Morikawa O
FAU - Gauldie, Jack
AU  - Gauldie J
FAU - Hara, Nobuyuki
AU  - Hara N
FAU - Mason, Robert J
AU  - Mason RJ
LA  - eng
GR  - HL56556/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20030619
PL  - United States
TA  - Am J Respir Cell Mol Biol
JT  - American journal of respiratory cell and molecular biology
JID - 8917225
RN  - 0 (Antibiotics, Antineoplastic)
RN  - 0 (Cytokines)
RN  - 0 (Receptors, Tumor Necrosis Factor)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Transforming Growth Factor beta)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 11056-06-7 (Bleomycin)
RN  - K7Q1JQR04M (Dinoprostone)
RN  - RMB44WO89X (Hydroxyproline)
SB  - IM
MH  - Adenoviridae/genetics/metabolism
MH  - Animals
MH  - Antibiotics, Antineoplastic/*pharmacology
MH  - Bleomycin/*pharmacology
MH  - Cytokines/metabolism
MH  - Dinoprostone/metabolism
MH  - Fibrosis/*metabolism
MH  - Genetic Vectors
MH  - Humans
MH  - Hydroxyproline/metabolism
MH  - Lung/cytology/*drug effects/metabolism/*pathology
MH  - Mice
MH  - Mice, Transgenic
MH  - Receptors, Tumor Necrosis Factor/genetics/metabolism
MH  - Recombinant Proteins/genetics/metabolism
MH  - Transforming Growth Factor beta/*pharmacology
MH  - Tumor Necrosis Factor-alpha/genetics/*metabolism
EDAT- 2003/06/21 05:00
MHDA- 2004/01/21 05:00
CRDT- 2003/06/21 05:00
PHST- 2003/06/21 05:00 [pubmed]
PHST- 2004/01/21 05:00 [medline]
PHST- 2003/06/21 05:00 [entrez]
AID - 2002-0046OC [pii]
AID - 10.1165/rcmb.2002-0046OC [doi]
PST - ppublish
SO  - Am J Respir Cell Mol Biol. 2003 Dec;29(6):669-76. doi: 10.1165/rcmb.2002-0046OC. 
      Epub 2003 Jun 19.