Protein SV-IV promotes nitric oxide production not associated with apoptosis in murine macrophages.
SV-IV (seminal vesicle protein no. 4) is a potent immunomodulatory and anti-inflammatory secretory protein (Mr 9758) produced in large amounts by the rat seminal vesicle epithelium. Here we show that this protein possesses the ability to upregulate in J774 macrophages the expression of the gene coding for the inducible nitric oxide synthase (iNOS). The increase in NO production consequent on the marked enhancement of iNOS activity was not associated with apoptotic damage of the SV-IV-treated cells. In the same experimental model, however, LPS induced upregulation of iNOS coupled with an increase in NO production and marked apoptotic death. Differences in the ability of SV-IV and LPS to control the life/ death signal balance in target cells via trans-membrane activation of apoptotic (mediated by TNF-alpha and NO/iNOS system) and anti-apoptotic (mediated by bcl-2, c-myc, etc.) pathways are suggested to be the basis of the apoptotic fate of the experimentally treated cells. In addition, considering the important role played by NO in the process of mammalian reproduction, SV-IV may be involved in the fine tuning of NO concentration in the female genital tract mucosa via an SV-IV-mediated control of iNOS gene expression in local macrophages.
Esposito
Carla
C
Department of Chemistry, University of Salerno, Italy.
Cozzolino
Anna
A
Porta
Raffaele
R
Mariniello
Loredana
L
Buommino
Elisabetta
E
Morelli
Francesco
F
Metafora
Vittoria
V
Metafora
Salvatore
S
D000818:Animals; D000906:Antibodies / Q000378:metabolism; D017209:Apoptosis / Q000502:physiology*; D002478:Cells, Cultured; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D020287:In Situ Nick-End Labeling; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D051379:Mice; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D051381:Rats; D011919:Rats, Inbred Strains; D029607:Seminal Vesicle Secretory Proteins / Q000494:pharmacology / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism
D000906:Antibodies; D008070:Lipopolysaccharides; D029607:Seminal Vesicle Secretory Proteins; C101178:Svs4 protein, rat; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C496318:Nos2 protein, rat