title: Effect of protein SV-IV on experimental Salmonella enterica serovar Typhimurium infection in mice.
abstract: Seminal vesicle protein IV (SV-IV) is a secretory anti-inflammatory, procoagulant, and immunomodulatory protein produced in large amounts by the seminal vesicle epithelium of the rat under the strict transcriptional control of androgen. In particular, this protein was shown to possess the ability to markedly inhibit in vivo the humoral and cell-mediated immune responses of mice to nonbacterial cellular antigens (sheep erythrocytes and spermatozoa). We report data that demonstrate that in mice treated with SV-IV and infected with Salmonella enterica serovar Typhimurium, SV-IV is able to downregulate some important immunological and biochemical parameters that serovar Typhimurium normally upregulates in these animals. This event did not correlate with a lower bacterial burden but was associated with a markedly increased one (300%). Furthermore, the treatment of mice with SV-IV alone also produced a significant increase in the rate of mortality among serovar Typhimurium-infected animals. The mechanism underlying these phenomena was investigated, and the strong immunosuppression produced by SV-IV in serovar Typhimurium-infected mice was suggested to be the basis for the increased rate of mortality. The SV-IV-mediated immunosuppression was characterized by a decrease in the humoral and cell-mediated immune responses, altered lymphocyte-macrophage interaction, downregulation of cytokine and inducible nitric oxide synthase gene expression, inhibition of macrophage phagocytosis and intracellular killing activities, and absence of apoptosis in the splenocyte population of SV-IV- and serovar Typhimurium-treated mice. The immunosuppressive activity of SV-IV was specific and was not due to aspecific cytotoxic effects. SV-IV-specific receptors (K(d) = 10(-8) M) occurring on the macrophage and lymphocyte plasma membranes may be involved in the molecular mechanism underlying the SV-IV-mediated immunosuppression. Some results obtained by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay also revealed a functional impairment of mitochondria (a decrease in mitochondrial dehydrogenase activity), thus indicating the possible implication of these organelles in the immunosuppressive process.
authors.affiliation: Institute of Microbiology, Department of Biochemistry and Biophysics, Medical School, 2nd University of Naples, Larghetto Santaniello a Caponapoli, 80138, Naples, Italy. caterina.romano@unina2.it
authors.forename: Caterina
authors.initials: C
authors.lastname: Romano-Carratelli
authors.forename: Concetta
authors.initials: C
authors.lastname: Bentivoglio
authors.forename: Immacolata
authors.initials: I
authors.lastname: Nuzzo
authors.forename: Nunzia
authors.initials: N
authors.lastname: Benedetto
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Buommino
authors.forename: Anna
authors.initials: A
authors.lastname: Cozzolino
authors.forename: Maria
authors.initials: M
authors.lastname: Cartenì
authors.forename: Francesco
authors.initials: F
authors.lastname: Morelli
authors.forename: Maria Rosaria
authors.initials: MR
authors.lastname: Costanza
authors.forename: Biancamaria
authors.initials: B
authors.lastname: Metafora
authors.forename: Vittoria
authors.initials: V
authors.lastname: Metafora
authors.forename: Salvatore
authors.initials: S
authors.lastname: Metafora
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D000917:Antibody Formation / Q000187:drug effects; D017209:Apoptosis; D016207:Cytokines / Q000235:genetics; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects; D017737:Macrophages, Peritoneal / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008928:Mitochondria / Q000473:pathology; D009569:Nitric Oxide / Q000096:biosynthesis; D019001:Nitric Oxide Synthase / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II; D010587:Phagocytosis; D012333:RNA, Messenger / Q000032:analysis; D012481:Salmonella Infections, Animal / Q000276:immunology*; D012486:Salmonella typhimurium; D029607:Seminal Vesicle Secretory Proteins / Q000494:pharmacology*
chemical_list: D000907:Antibodies, Bacterial; D016207:Cytokines; D007166:Immunosuppressive Agents; D012333:RNA, Messenger; D029607:Seminal Vesicle Secretory Proteins; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse