PMID- 9048615
OWN - NLM
STAT- MEDLINE
DCOM- 19970407
LR  - 20181130
IS  - 0013-7227 (Print)
IS  - 0013-7227 (Linking)
VI  - 138
IP  - 3
DP  - 1997 Mar
TI  - Tumor necrosis factor-alpha regulates plasminogen activator inhibitor-1 in rat 
      testicular peritubular cells.
PG  - 1097-105
AB  - We examined the regulation by tumor necrosis factor-alpha (TNF alpha) of 
      plasminogen activator inhibitor-1 (PAI-1) in cultured peritubular cells recovered 
      from 20-day-old rat testes. We demonstrated that TNF alpha in a nanomolar dose 
      range stimulated PAI-1 messenger RNA (mRNA; Northern blots) as well as 
      immunoreactive (Western blots) and bioactive (Stachrom) PAI-1 protein. Induction 
      of PAI-1 mRNA started 4 h after the addition of TNF alpha (2.5-fold increase) and 
      peaked (7-fold increase) after 24 h of treatment. Actinomycin D and cycloheximide 
      inhibited the effects of TNF alpha on PAI-1 mRNA, suggesting that ongoing RNA and 
      protein syntheses were required. The combined actions of transforming growth 
      factor-alpha (TGF alpha), a potent inducer of PAI-1, and TNF alpha on PAI-1 were 
      less than additive, suggesting the activation of some common pathway. TNF alpha 
      action on PAI-1, like that of TGF alpha demonstrated previously, was masked by a 
      preexposure to phorbol myristate acetate (a stimulator of protein kinase C) and 
      strongly reduced by staurosporine (an inhibitor of the protein kinase C). 
      Furthermore, using genistein to inhibit tyrosine kinase activity, we not only 
      blocked the action of TGF alpha on PAI-1 [initiated upon binding to the tyrosine 
      kinase epidermal growth factor/TGF alpha receptor (EGFR)], but also markedly 
      reduced that of TNF alpha. Finally, TNF alpha, at a dose range that stimulated 
      PAI-1, enhanced EGFR mRNA levels and EGF binding. Together, the present findings 
      suggest that some of the biological effects of TNF alpha on PAI-1 might be 
      secondary to de novo synthesis of EGFR. Because TNF alpha probably originates 
      from testicular macrophages, such a regulation of PAI-1 by TNF alpha may occur in 
      the context of physiological interactions between the testis and the immune 
      system.
FAU - Le Magueresse-Battistoni, B
AU  - Le Magueresse-Battistoni B
AD  - INSERM U-407, Batiment 3B, Centre Hospitalier Lyon-Sud, Pierre-Benite, France.
FAU - Pernod, G
AU  - Pernod G
FAU - Kolodie, L
AU  - Kolodie L
FAU - Morera, A M
AU  - Morera AM
FAU - Benahmed, M
AU  - Benahmed M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Endocrinology
JT  - Endocrinology
JID - 0375040
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Isoflavones)
RN  - 0 (Plasminogen Activator Inhibitor 1)
RN  - 0 (Protein Synthesis Inhibitors)
RN  - 0 (RNA, Messenger)
RN  - 0 (Transforming Growth Factor alpha)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 1CC1JFE158 (Dactinomycin)
RN  - 62229-50-9 (Epidermal Growth Factor)
RN  - 98600C0908 (Cycloheximide)
RN  - DH2M523P0H (Genistein)
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - H88EPA0A3N (Staurosporine)
RN  - NI40JAQ945 (Tetradecanoylphorbol Acetate)
SB  - IM
MH  - Animals
MH  - Cells, Cultured
MH  - Cycloheximide/pharmacology
MH  - Dactinomycin/pharmacology
MH  - Enzyme Inhibitors/pharmacology
MH  - Epidermal Growth Factor/metabolism
MH  - ErbB Receptors/genetics
MH  - Genistein
MH  - Isoflavones/pharmacology
MH  - Male
MH  - Plasminogen Activator Inhibitor 1/genetics/*metabolism
MH  - Protein Synthesis Inhibitors/pharmacology
MH  - RNA, Messenger/metabolism
MH  - Rats
MH  - Staurosporine/pharmacology
MH  - Testis/cytology/drug effects/*metabolism
MH  - Tetradecanoylphorbol Acetate/pharmacology
MH  - Transforming Growth Factor alpha/pharmacology
MH  - Tumor Necrosis Factor-alpha/*pharmacology
MH  - Up-Regulation
EDAT- 1997/03/01 00:00
MHDA- 1997/03/01 00:01
CRDT- 1997/03/01 00:00
PHST- 1997/03/01 00:00 [pubmed]
PHST- 1997/03/01 00:01 [medline]
PHST- 1997/03/01 00:00 [entrez]
AID - 10.1210/endo.138.3.4963 [doi]
PST - ppublish
SO  - Endocrinology. 1997 Mar;138(3):1097-105. doi: 10.1210/endo.138.3.4963.