PMID- 15538942
OWN - NLM
STAT- MEDLINE
DCOM- 20041228
LR  - 20190906
IS  - 0804-4643 (Print)
IS  - 0804-4643 (Linking)
VI  - 151
IP  - 5
DP  - 2004 Nov
TI  - Tumor necrosis factor-alpha (TNF-alpha) promotes cell survival during 
      spermatogenesis, and this effect can be blocked by infliximab, a TNF-alpha 
      antagonist.
PG  - 629-40
AB  - OBJECTIVE: Tumor necrosis factor-alpha (TNF-alpha) has been shown to inhibit germ 
      cell death in human seminiferous epithelium. In the present study, we wanted to 
      explore the effects of TNF-alpha in the rat seminiferous epithelium and to study 
      molecular mechanisms of germ cell apoptosis. Furthermore, the effects of 
      infliximab were studied. Infliximab is a TNF-alpha antagonist used in autoimmune 
      disorders, such as rheumatoid arthritis and Crohn's disease. METHODS: Rat 
      seminiferous tubule segments were cultured in the presence and absence of 
      TNF-alpha, infliximab and SN50, a NF-kappa B inhibitor. TUNEL-staining and 
      cleaved caspase-3 immunohistochemistry combined with squash preparations of rat 
      seminiferous tubule segments were used to evaluate the number of apoptotic cells. 
      Western blot analyses were performed on cultured seminiferous tubule segments for 
      Bcl-2 family proteins (Bax, Bad, Bcl-w, Bcl-xL) and fas ligand. RESULTS: 
      TNF-alpha promotes cell survival in the rat seminiferous epithelium, and this 
      prosurvival effect can be blocked by infliximab, a TNF-alpha antagonist. Bcl-xL 
      was found to be upregulated in mitochondrial membranes by TNF-alpha, and this 
      upregulation was inhibited by infliximab. Inhibition of NF-kappa B translocation 
      to the nucleus prevented the prosurvival effect of TNF-alpha on seminiferous 
      epithelium. CONCLUSIONS: The present study demonstrates that TNF-alpha promotes 
      cell survival in the rat seminiferous epithelium, and this effect can be blocked 
      by infliximab. This is the first study to show the effects of infliximab in the 
      testis. The prosurvival effect of TNF-alpha might be at least partly mediated by 
      modulating the expression and subcellular localization of Bcl-2 family proteins.
FAU - Suominen, Janne S
AU  - Suominen JS
AD  - Departments of Physiology and Pediatrics, University of Turku, Turku, Finland.
FAU - Wang, Yangyang
AU  - Wang Y
FAU - Kaipia, Antti
AU  - Kaipia A
FAU - Toppari, Jorma
AU  - Toppari J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Eur J Endocrinol
JT  - European journal of endocrinology
JID - 9423848
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Bcl2l1 protein, rat)
RN  - 0 (NF-kappa B)
RN  - 0 (Peptides)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - 0 (SN50 peptide)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (bcl-X Protein)
RN  - B72HH48FLU (Infliximab)
SB  - IM
MH  - Active Transport, Cell Nucleus/drug effects
MH  - Animals
MH  - Antibodies, Monoclonal/*pharmacology
MH  - Apoptosis
MH  - Cell Survival/drug effects
MH  - Dose-Response Relationship, Drug
MH  - Infliximab
MH  - Male
MH  - Mitochondria/metabolism
MH  - NF-kappa B/antagonists & inhibitors/metabolism
MH  - Peptides/pharmacology
MH  - Proto-Oncogene Proteins c-bcl-2/antagonists & inhibitors/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Seminiferous Tubules/cytology/*physiology
MH  - Spermatogenesis/*physiology
MH  - Tumor Necrosis Factor-alpha/administration & dosage/*antagonists & 
      inhibitors/*pharmacology
MH  - bcl-X Protein
EDAT- 2004/11/13 09:00
MHDA- 2004/12/29 09:00
CRDT- 2004/11/13 09:00
PHST- 2004/11/13 09:00 [pubmed]
PHST- 2004/12/29 09:00 [medline]
PHST- 2004/11/13 09:00 [entrez]
AID - 10.1530/eje.0.1510629 [doi]
PST - ppublish
SO  - Eur J Endocrinol. 2004 Nov;151(5):629-40. doi: 10.1530/eje.0.1510629.