Extracellular inosine participates in tumor necrosis factor-alpha induced nitric oxide production in cultured Sertoli cells.
Recent reports have described purinergic modulation of tumor necrosis factor-alpha (TNF-alpha) signaling in neutrophils and astrocytes. In Sertoli cells, both TNF-R1 and TNF-R2 TNF-alpha receptors are present and this cytokine modulates many functions of these cells related to the maintenance of spermatogenesis. Sertoli cells express distinct purinoreceptors and previous work has shown that these cells secrete extracellular nucleotides and their metabolites. In this work, we studied the possible role of extracellular purines in TNF-alpha signaling in cultured Sertoli cells. This cytokine increased inosine concentration from 30 min to 6 h, with no effect at 24 h. Both TNF-alpha and inosine increased nitrite accumulation and nitric oxide synthase activity. Erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA), an adenosine deaminase inhibitor, abolished the TNF-alpha induced inosine increase, nitrite accumulation and nitric oxide synthase activity. These results suggest that extracellular inosine acts as intermediary in TNF-alpha stimulated nitric oxide production in cultured Sertoli cells.
de Souza
Luiz Fernando
LF
Laboratório de Transdução de Sinais em Células Testiculares, Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
Gelain
Daniel Pens
DP
Jardim
Fernanda Rafaela
FR
Ribeiro
Gisele Roncheti
GR
Zim
Marcelo
M
Bernard
Elena Aida
EA
D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D058892:Adenosine Deaminase Inhibitors; D000818:Animals; D002478:Cells, Cultured; D005110:Extracellular Space / Q000502:physiology*; D007288:Inosine / Q000502:physiology*; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar; D012708:Sertoli Cells / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
D058892:Adenosine Deaminase Inhibitors; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; C010192:9-(2-hydroxy-3-nonyl)adenine; D007288:Inosine; D000225:Adenine