Anti-apoptotic seminal vesicle protein IV inhibits cell-mediated immunity

Fuggetta, Maria Pia; Lanzilli, Giulia; Cottarelli, Andrea; Ravagnan, Giampietro; Cartenı̀, Maria; Maria, S. De; Metafora, Bianca M.; Metafora, Vittoria; Metafora, Salvatore

doi:10.1016/j.jri.2007.11.002

Cited by 4 publications

(9 citation statements)

References 31 publications

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“…These results: (a) are in line with the antiapoptotic and immunosuppressive properties of SV-IV [13,17,19,20,21,22,23,24,28]; (b) confirm a modulatory activity of this protein on mammal inflammation reactivity by either inhibiting the arachidonate cascade pathway [19,21] or stimulating the release of proinflammatory cytokines from lymphocytes/monocytes [13] and histamine from FcεRI+ cells; (c) raise the possibility of a protective role of SV-IV on implanting hemiallogenic blastocyst against reactive oxygen species and maternal immunological attacks at the uterine implantation site in concert with other local immunosuppressive cells (mast cells and CD4+CD25+ FoxP3+ regulatory T cells), cytokines (TGF-β 1 , IL-10), and antiapoptotic factors (leukemia inhibitory factor, heme oxygenase 1, peroxidases and histamine).…”

Section: Introductionsupporting

confidence: 67%

“…The possibility that histamine release induced by SV-IV could be related to a generic toxicity or a proapoptotic effect of SV-IV on its target cells is, however, ruled out by several published data showing that SV-IV is nontoxic and strongly antiapoptotic [17,28]. In addition, treatment of FcεRI+ cells with 10–30 µ M SV-IV in short- and long-time incubations does not produce any significant change in cell viability, as measured by the LDH assay.…”

Section: Discussionmentioning

confidence: 99%

“…The presence of the immunosuppressive and antiapoptotic SV-IV in uterus at the implantation site [28] could contribute to the definition of the immunotolerant characteristics of the site. However, evidence that SV-IV is present in this location is only circumstantial: (a) SV-IV is present in rat ejaculated semen in free and sperm-bound form; (b) an SV-IV immunorelated protein has been found in rat uterine lysates and in human seminal plasma [1,14,15,16,55,56].…”

Section: Discussionmentioning

confidence: 99%

“…However, evidence that SV-IV is present in this location is only circumstantial: (a) SV-IV is present in rat ejaculated semen in free and sperm-bound form; (b) an SV-IV immunorelated protein has been found in rat uterine lysates and in human seminal plasma [1,14,15,16,55,56]. In rats, this speculation is supported by experiments demonstrating that the immunogenicity of blastocyst blastomeres is suppressed (about 80%) by SV-IV [28]. These SV-IV-induced immunosuppressive findings are in line with: (a) the ability of SV-IV to activate mast cell and basophil degranulation with release of immunosuppressive and antiapoptotic histamine [[38] and our data reported in this article]; (b) the ability of SV-IV to protect mouse zygote growth up to the blastocyst stage [17]; (c) other data showing the critical role of oxidative stress in jeopardizing embryo survival during early development [57], and (d) the protective effect of SV-IV on some target cancer cells (Raji, K562, DAUDI) against NK cytotoxicity [28].…”

Section: Discussionmentioning

confidence: 99%

“…Besides, SV-IV immunosuppressive properties suggest a defensive role against maternal immunological attack of hemiallogenic implanting blastocysts [11,19,23,25,27]. The anti-inflammatory effect of the protein is related to phospholipase A 2 (PLA 2 ) inhibition, while its immunomodulatory activity is generated by interference with macrophage-T cell cooperation (modulation of cytokine production; inhibition of macrophage antigen presentation and T cell activation) [13,19,20,21,22,23,24,28]. …”

Section: Introductionmentioning

confidence: 99%

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Antiapoptotic Seminal Vesicle Protein IV Induces Histamine Release from Human FcεRI+ Cells

Prevete

Rossi

Triggiani

et al. 2009

Int Arch Allergy Immunol

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Background: Seminal vesicle protein number 4 (SV-IV) is a small, basic, multifunctional, intrinsically disordered secretory protein synthesized in large amounts by rat seminal vesicle epithelium under androgen transcriptional control. SV-IV-immunorelated proteins occur in other rat tissues and in humans. Methods: The in vitro effect of SV-IV on human FcΕRI+ cells was investigated by standard immunologic, biochemical and molecular biology procedures. Results: SV-IV-induced histamine release from human basophils and lung mast cells without any influence on leukotriene C₄ release and cell migration. The histamine release rate was slower compared with that induced by anti-IgE, the temperature dependence of the event being similar. SV-IV-induced histamine release was Ca²⁺-dependent, suggesting a physiological interaction of the protein with FcΕRI+ cells. SV-IV and anti-IgE acted synergistically on the histamine release. SV-IV did not induce de novo synthesis of cytokines and growth factors (transforming growth factor-β₁, interleukin-10, interleukin-13, tumor necrosis factor-α, vascular endothelial growth factor A) in FcΕRI+ cells. Conclusions: SV-IV protein induces in human FcΕRI+ cells the release of histamine, a proinflammatory, antiapoptotic and immunosuppressive biogenic amine. These data: (1) are consistent with the antiapoptotic and immunosuppressive properties of SV-IV; (2) confirm a regulatory feature of SV-IV on mammal inflammatory reactivity by either inhibiting the arachidonate cascade pathway or stimulating proinflammatory cytokine release from lymphocyte/monocytes and histamine from FcΕRI+ cells; (3) raise the possibility of a protective role of SV-IV on implanting hemiallogenic blastocysts against maternal reactive oxygen species and immunological attacks at the uterine implantation site.

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Section: Introductionsupporting

confidence: 67%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Antiapoptotic Seminal Vesicle Protein IV Induces Histamine Release from Human FcεRI+ Cells

Prevete

Rossi

Triggiani

et al. 2009

Int Arch Allergy Immunol

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Interferon-Beta Combined with Interleukin-2 Restores Human Natural Cytotoxicity ImpairedIn Vitroby Ionizing Radiations

Franzese

Tricarico

Starace

et al. 2013

Journal of Interferon & Cytokine Research

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It is well known that ionizing radiations induce a marked downregulation of antigen-dependent and natural immunity for a prolonged period of time. This is due, at least in part, to radiation-induced apoptosis of different lymphocyte subpopulations, including natural killer (NK) cells. Aim of this study was to investigate the capability of Beta Interferon (β-IFN) and Interleukin-2 (IL2), alone or in combination, to restore the functional activity of the natural immune system. Mononuclear cells (MNCs) obtained from intact or in vitro irradiated human peripheral blood were treated in vitro with β-IFN immediately before or at the end of the 4-day treatment with IL2. Time-course analysis was performed on the NK activity, the total number and the apoptotic fraction of CD16+ and CD56+ cells, the 2 main NK effector cell subpopulations. The results indicate that radiation-induced impairment of natural cytotoxicity of MNC could be successfully antagonized by the β-IFN+IL2 combination, mainly when exposure to β-IFN preceded IL2 treatment. This radioprotective effect is paralleled by lower levels of radiation-induced apoptosis and increased expression of the antiapoptotic Bcl-2 protein. Since natural immunity can play a significant role in antitumor host's resistance, these results could provide the rational basis for a cytokine-based pharmacological strategy able to restore immune responsiveness and to afford possible therapeutic benefits in cancer patients undergoing radiotherapy.

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In vitro stimulatory effect of anti‐apoptotic seminal vesicle protein 4 on purified peroxidase enzymes

et al. 2008

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The enzymatic activities of purified horseradish peroxidase, selenium-dependent glutathione peroxidase, thyroid peroxidase and myeloperoxidase, but not that of lactoperoxidase, were markedly enhanced when added into a reaction mixture containing 5 lm native seminal vesicle protein 4, a major protein secreted from rat seminal vesicle epithelium. A further increase of horseradish peroxidase activity was obtained using Ser58-phosphorylated or acetylated seminal vesicle protein 4. The activating effect of native seminal vesicle protein 4 was highest (about 60-fold) on horseradish peroxidase when 4-chloro-1-naphtol was used as the electron donor substrate. The main kinetics parameters of the stimulatory effect on horseradish peroxidase were evaluated and the enzyme-electron donor substrate interaction was investigated by HPLC and electrospray-MS. A native seminal vesicle protein 4 ⁄ 4-chloro-1-naphtol noncovalent adduct was detected when the protein and 4-chloro-1-naphtol were present in the appropriate molar ratio in the horseradish peroxidase-catalyzed reaction. By contrast, no adducts were formed between native seminal vesicle protein 4 and horseradish peroxidase. This native seminal vesicle protein 4 ⁄ 4-chloro-1-naphtol interaction might underlie the native seminal vesicle protein 4-induced horseradish peroxidase stimulation. Furthermore, native seminal vesicle protein 4 was shown by spectrophotometric and electrospray-MS analysis to interact with NADPH, an electron donor substrate of the selenium-dependent glutathione peroxidase ⁄ glutathione reductase redox system, with formation of an adduct between them. Although further investigation is required to elucidate the mechanism of adduct formation, this interaction, probably by promoting the release of the NADPH electrons required for glutathione disulphide reduction, could explain the stimulatory effect of seminal vesicle protein 4 on mammalian peroxidases possibly involved in its physiological function on the selenium-dependent glutathione peroxidase ⁄ glutathione reductase system. The biological significance of these properties of native seminal vesicle protein 4 might be related to its ability to downregulate reactive oxygen species and oxidative stress-induced apoptosis.Abbreviations DAB, diaminobenzidine 4HCl; EDS, electron donor substrate; GPX, selenium-dependent glutathione peroxidase; GR, glutathione reductase; GSH, reduced glutathione; GUA, guaiacol; HRP, horseradish peroxidase; LPO, lactoperoxidase; MPO, myeloperoxidase; NAP, 4-chloro-1-napthtol; nSV-IV, native seminal vesicle protein 4; ROS, reactive oxygen species; SV-IV, seminal vesicle protein 4; SV-IVp, phosphorylated seminal vesicle protein 4; TPO, thyroid peroxidase.

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Anti-apoptotic seminal vesicle protein IV inhibits cell-mediated immunity

Abstract: The in vitro effect of the seminal vesicle protein IV (SV-IV) on the cytotoxic activity of human natural or acquired cellular immunity has been investigated by standard immunological procedures, a 51 Cr-release cytotoxicity assay, and

Cited by 4 publications

References 31 publications

Antiapoptotic Seminal Vesicle Protein IV Induces Histamine Release from Human FcεRI+ Cells

Antiapoptotic Seminal Vesicle Protein IV Induces Histamine Release from Human FcεRI+ Cells

Interferon-Beta Combined with Interleukin-2 Restores Human Natural Cytotoxicity ImpairedIn Vitroby Ionizing Radiations

In vitro stimulatory effect of anti‐apoptotic seminal vesicle protein 4 on purified peroxidase enzymes

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