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Abstract:

Problem: Impaired pregnancy in non-obese diabetic (NOD) mice was related to limited vascular remodeling and autoimmune background. Vasoactive intestinal peptide (VIP) has anti-inflammatory and immunosuppressant effects, so we explored its ability to modulate the immune microenvironment at the early maternal-placental interface and improve pregnancy in NOD mice. Method of study: Implantation sites were isolated from pregnant NOD mice at gestational day 9.5 and were incubated with VIP for evaluation of cytokine or transcription factor expression by RT-PCR, immunoblotting, and immunohistochemistry. Alternatively, pregnant mice were injected with VIP at day 6.5 and studied at day 9.5. Results: VIP and VPAC receptors were detected in viable implantation sites. VIP immunostaining was found predominantly on trophoblast giant cells. The in vitro treatment of viable implantation sites with VIP increased IL-10, TGF-β, and Foxp3 expression. Sites with resorption processes presented lower VIP expression, reduced suppressant markers, and increased IL-17 and RORγT expression compared with viable sites and VIP reduced RORγT expression. Pregnant mice treated with VIP at day 6.5 presented an even distribution of viable implantation sites with an increased expression of IL-10, TGF- β, and Foxp3. Conclusion: VIP induces an immunosuppressant profile at the early maternal-placental interface of NOD mice and improves pregnancy outcome. © 2013 John Wiley & Sons Ltd.

Registro:

Documento: Artículo
Título:Vasoactive Intestinal Peptide Induces an Immunosuppressant Microenvironment in the Maternal-Fetal Interface of Non-Obese Diabetic Mice and Improves Early Pregnancy Outcome
Autor:Hauk, V.; Azzam, S.; Calo, G.; Gallino, L.; Paparini, D.; Franchi, A.; Ramhorst, R.; Leirós, C.P.
Filiación:Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, IQUIBICEN-CONICET, Buenos Aires, Argentina
Facultad de Medicina, Universidad de Buenos Aires, CEFYBO-CONICET, Buenos Aires, Argentina
Idioma: Inglés
Palabras clave:Early pregnancy; Foxp3; IL-10; non-obese diabetic mice; TGF-β; Vasoactive intestinal peptide
Año:2014
Volumen:71
Número:2
Página de inicio:120
Página de fin:130
DOI: http://dx.doi.org/10.1111/aji.12167
Título revista:American Journal of Reproductive Immunology
Título revista abreviado:Am. J. Reprod. Immunol.
ISSN:10467408
CODEN:AAJID
Registro:http://digital.bl.fcen.uba.ar/collection/paper/document/paper_10467408_v71_n2_p120_Hauk

Referencias:

  • Gomez-Lopez, N., Guilbert, L., Olson, D.M., Invasion of the leukocytes into the fetal-maternal interface during pregnancy (2010) J Leukoc Biol, 88, pp. 625-633
  • Mor, G., Cardenas, I., The immune system in pregnancy: a unique complexity (2010) Am J Reprod Immunol, 63, pp. 425-433
  • Redman, C.W., Sargent, I.L., Immunology of pre-eclampsia (2010) Am J Reprod Immunol, 63, pp. 534-543
  • Dekel, N., Gnainsky, Y., Granot, I., Inflammation and implantation (2010) Am J Reprod Immunol, 63, pp. 17-21
  • Girardi, G., Yarlini, D., Thurman, J.M., Holers, V.M., Salmon, J.E., Complement activation induces dysregulation of angiogenic factors and causes fetal rejection and growth restriction (2006) J Exp Med, 203, pp. 2165-2175
  • Kwak-Kim, J., Yang, K., Gilman-Sachs, A., Recurrent pregnancy loss: a disease of inflammation and coagulation (2009) J Obstet Gynaecol Res, 35, pp. 609-622
  • Aluvihare, V.R., Kallikourdis, M., Betz, A.G., Regulatory T cells mediate maternal tolerance to the fetus (2004) Nat Immunol, 5, pp. 266-271
  • Saito, S., Shima, T., Nakashima, A., Shiozaki, A., Ito, M., Sasaki, Y., What is the role of regulatory T cells in the success of implantation and early pregnancy? (2007) J Assist Reprod Genet, 24, pp. 379-386
  • Zenclussen, A.C., Gerlof, K., Zenclussen, M.L., Sollwedel, A., Bertoja, A.Z., Ritter, T., Kotsch, K., Volk, H.-D., Abnormal T-cell reactivity against paternal antigens in spontaneous abortion: adoptive transfer of pregnancy-induced CD4 + CD25 + T regulatory cells prevents fetal rejection in a murine abortion model (2005) Am J Pathol, 166, pp. 811-822
  • Zenclussen, A.C., Adaptive immune responses during pregnancy (2013) Am J Reprod Immunol, 69, pp. 291-303
  • Teles, A., Zenclussen, A.C., Schumacher, A., Regulatory T cells are baby's best friends (2013) Am J Reprod Immunol, 69, pp. 331-339
  • Abrahams, V.M., Kim, Y.M., Straszewski, S.L., Romero, R., Mor, G., Macrophages and apoptotic cell clearance during pregnancy (2004) Am J Reprod Immunol, 51, pp. 275-282
  • Fest, S., Aldo, P.B., Abrahams, V.M., Visintin, I., Alvero, A., Chen, R., Chavez, S.L., Mor, G., Trophoblast-macrophage interactions: a regulatory network for the protection of pregnancy (2007) Am J Reprod Immunol, 57, pp. 55-66
  • Nagamatsu, T., Schust, D.J., The contribution of macrophages to normal and pathological pregnancies (2010) Am J Reprod Immunol, 63, pp. 460-471
  • Delaleu, N.N.C., Peck, A.B., Jonsson, R., Sjögren's syndrome: studying the disease in mice (2011) Arthritis Res Ther, 13, p. 217
  • Rosignoli, F., Roca, V., Meiss, R., Leceta, J., Gomariz, R.P., Pérez, L.C., Defective signalling in salivary glands precedes the autoimmune response in the non-obese diabetic mouse model of sialadenitis (2005) Clin Exp Immunol, 142, pp. 411-418
  • Jonsson, M.V., Delaleu, N., Brokstad, K., Berggreen, E., Skarstein, K., Impaired salivary gland function in NOD mice: association with changes in cytokine profile but not with histopathologic changes in the salivary gland (2006) Arthritis Rheum, 54, pp. 2300-2305
  • Burke, S.D., Dong, H., Hazan, A.D., Croy, B.A., Aberrant endometrial features of pregnancy in diabetic NOD mice (2007) Diabetes, 56, pp. 2919-2926
  • Lin, Y., Xu, L., Jin, H., Zhong, Y., Di, J., Lin, Q.D., CXCL12 enhances exogenous CD4+ CD25+ T cell migration and prevents embryo loss in non-obese diabetic mice (2009) Fertil Steril, 91, pp. 2687-2696
  • Roca, V., Calafat, M., Larocca, L., Ramhorst, R., Farina, M., Franchi, A.M., Pérez Leirós, C., Potential immunomodulatory role of VIP in the implantation sites of prediabetic nonobese diabetic mice (2009) Reproduction, 138, pp. 733-742
  • Li, W., Li, B., Fan, W., Geng, L., Li, X., Li, L., Huang, Z., Li, S., CTLA4Ig gene transfer alleviates abortion in mice by expanding CD4 + CD25 + regulatory T cells and inducing indoleamine 2,3-dioxygenase (2009) J Reprod Immunol, 80, pp. 1-11
  • Larocca, L., Calafat, M., Roca, V., Franchi, A.M., Pérez, C., VIP limits LPS-induced nitric oxide production through IL-10 in NOD mice macrophages (2007) Int Immunopharmacol, 7, pp. 1343-1349
  • Larocca, L., Hauk, V., Calafat, M., Roca, V., Fraccaroli, L., Franchi, A., Ramhorst, R., Leirós, C.P., Modulation of macrophage inflammatory profile in pregnant nonobese diabetic (NOD) mice (2011) Mol Cell Endocrinol, 333, pp. 112-118
  • Couvineau, A., Laburthe, M., VPAC receptors: structure, molecular pharmacology and interaction with accessory proteins (2011) Br J Pharmacol, 166, pp. 42-50
  • Ekström, J., Mansson, B., Tobin, G., Vasoactive intestinal peptide evoked secretion of fluid and protein from rat salivary glands and the development of supersensitivity (1983) Acta Physiol Scand, 119, pp. 169-175
  • Bjøro, T., Sand, O., Ostberg, B.C., Gordeladze, J.O., Torjesen, P., Gautvik, K.M., Haug, E., The mechanisms by which vasoactive intestinal peptide (VIP) and thyrotropin releasing hormone (TRH) stimulate prolactin release from pituitary cells (1990) Biosci Rep, 10, pp. 189-199
  • Deutsch, P.J.S.Y., Sun, Y., Kroog, G.S., Vasoactive intestinal peptide increases intracellular cAMP and gonadotropin-alpha gene activity in JEG-3 syncytial trophoblasts (1990) J Biol Chem, 265, pp. 10274-10281
  • Marzioni, D., Fiore, G., Giordano, A., Nabissi, M., Florio, P., Verdenelli, F., Petraglia, F., Castellucci, M., Placental expression of substance P and vasoactive intestinal peptide: evidence for a local effect on hormone release (2005) J Clin Endocrinol Metab, 90, pp. 2378-2383
  • Jovanovic, S.G.L., Grbovic, L., Jovanovic, A., Pregnancy does not alter the response of uterine arteries to vasoactive intestinal polypeptide (2000) Mol Hum Reprod, 6, pp. 361-368
  • Hill, J.M., McCune, S.K., Alvero, R.J., Glazner, G.W., Henins, K.A., Stanziale, S.F., Keimowitz, J.R., Brenneman, D.E., Maternal Vasoactive Intestinal Peptide and the Regulation of Embryonic Growth in the Rodent (1996) Measurement, 97, pp. 202-208
  • Passemard, S., Sokolowska, P., Schwendimann, L., Gressens, P., VIP-induced neuroprotection of the developing brain (2011) Curr Pharm Des, 17, pp. 1036-1039
  • Gomariz, R.P., Arranz, A., Juarranz, Y., Gutierrez-Cañas, I., Garcia-Gomez, M., Leceta, J., Martínez, C., Regulation of TLR expression, a new perspective for the role of VIP in immunity (2007) Peptides, 28, pp. 1825-1832
  • Gonzalez-Rey, E., Delgado, M., Vasoactive intestinal peptide and regulatory T-cell induction: a new mechanism and therapeutic potential for immune homeostasis (2007) Trends Mol Med, 13, pp. 241-251
  • Delgado, M., Munoz-Elias, E.J., Martinez, C., Gomariz, R.P., Ganea, D., VIP and PACAP38 modulate cytokine and nitric oxide production in peritoneal macrophages and macrophage cell lines (1999) Ann N Y Acad Sci, 897, pp. 401-414
  • Roca, V., Larocca, L., Calafat, M., Aisemberg, J., Meiss, R., Franchi, A.M., Pérez Leirós, C., Reduced nitric oxide synthase and cyclo-oxygenase activity in the uterus of non-obese diabetic mice (2006) Reproduction (Cambridge, England), 132, pp. 931-938
  • Hauk, V., Calafat, M., Larocca, L., Fraccaroli, L., Grasso, E., Ramhorst, R., Perez Leirós, C., Vasoactive intestinal peptide/vasoactive intestinal peptide receptor relative expression in salivary glands as one endogenous modulator of acinar cell apoptosis in a murine model of Sjögren's syndrome (2011) Clin Exp Immunol, 166, pp. 309-316
  • Tsukada, T., Fink, J.S., Mandel, G., Goodman, R.H., Identification of a region in the human vasoactive intestinal polypeptide gene responsible for regulation by cyclic AMP (1987) J Biol Chem, 262, pp. 8743-8747
  • Lin, Y., Ren, L., Wang, W., Di, J., Zeng, S., Saito, S., Effect of TLR3 and TLR7 activation in uterine NK cells from non-obese diabetic (NOD) mice (2009) J Reprod Immunol, 82, pp. 12-23
  • Li, C., Wang, W., Wang, H., Zhong, Y., Di, J., Lin, Y., Proteomic analysis of proteins differentially expressed in uterine lymphocytes obtained from wild-type and NOD mice (2009) J Cell Biolchem, 108, pp. 447-457
  • Hill, J.M., Cuasay, K., Abebe, D.T., Vasoactive intestinal peptide antagonist treatment during mouse embryogenesis impairs social behavior and cognitive function of adult male offspring (2007) Exp Neurol, 206, pp. 101-113
  • Spong, C.Y., Lee, S.J., Cune, S.K.M.C., Gibney, G., Abebe, D.T., Alvero, R., Brenneman, D.E., Hill, J.M., Maternal regulation of embryonic growth: the role of vasoactive intestinal peptide (1999) Endocrinology, 140, pp. 917-924
  • Gressens, P., Marret, S., Hill, J.M., Brenneman, D.E., Gozes, I., Fridkin, M., Evrard, P., Vasoactive intestinal peptide prevents excitotoxic cell death in the murine developing brain (1997) J Clin Invest, 100, pp. 390-397
  • Rangon, C.-M., Dicou, E., Goursaud, S., Mounien, L., Jégou, S., Janet, T., Muller, J.-M., Gressens, P., Mechanisms of VIP-induced neuroprotection against neonatal excitotoxicity (2006) Ann N Y Acad Sci, 1070, pp. 512-517
  • Fraccaroli, L., Alfieri, J., Larocca, L., Calafat, M., Roca, V., Lombardi, E., Ramhorst, R., Pérez Leirós, C., VIP modulates the pro-inflammatory maternal response inducing tolerance to trophoblast cells (2009) Br J Pharmacol, 156, pp. 116-126
  • Fraccaroli, L., Grasso, E., Zeitler, E., Lombardi, E., Gogorza, S., Etchepareborda, J.J., Nagle, C., Ramhorst, R., Modulation of maternal LIF producers T cells by trophoblast and paternal antigens (2010) Am J Reprod Immunol, 65, pp. 133-145
  • Sallusto, F., Zielinski, C.E., Lanzavecchia, A., Human Th17 subsets (2012) Eur J Immunol, 42, pp. 2215-2220
  • Veldhoen, M., Stockinger, B., TGFbeta1, a "Jack of all trades": the link with pro-inflammatory IL-17-producing T cells (2006) Trends Immunol, 27, pp. 358-361
  • Nikoopour, E., Schwartz, J.A., Huszarik, K., Sandrock, C., Krougly, O., Lee-Chan, E., Singh, B., Th17 polarized cells from nonobese diabetic mice following mycobacterial adjuvant immunotherapy delay type 1 diabetes (2010) J Immunol, 184, pp. 4779-4778
  • Larocca, L., Roca, V., Neuroimmune-Endocrine Interactions during Early Pregnancy in an Autoimmune Context: Focus on Macrophage Activation (2008) NeuroImmunoModulation, 15, pp. 84-90
  • Kohmura, Y., Kirikae, T., Kirikae, F., Nakano, M., Sato, I., Lipopolysaccharide (LPS)-induced intra-uterine fetal death (IUFD) in mice is principally due to maternal cause but not fetal sensitivity to LPS (2000) Microbiol Immunol, 44, pp. 897-904
  • Durant, S., Christeff, N., Coulaud, J., Nunez, E.A., Dardenne, M., Homo-Delarche, F., Basal concentrations of various steroids in the nonobese diabetic (NOD) mouse and effect of immobilization stress (1998) Autoimmunity, 28, pp. 249-258
  • Homo-Delarche, F., Neuroendocrine immuno-ontogeny of the pathogenesis of autoimmune disease in the nonobese diabetic (NOD) mouse (2004) ILAR J, 45, pp. 237-258

Citas:

---------- APA ----------
Hauk, V., Azzam, S., Calo, G., Gallino, L., Paparini, D., Franchi, A., Ramhorst, R.,..., Leirós, C.P. (2014) . Vasoactive Intestinal Peptide Induces an Immunosuppressant Microenvironment in the Maternal-Fetal Interface of Non-Obese Diabetic Mice and Improves Early Pregnancy Outcome. American Journal of Reproductive Immunology, 71(2), 120-130.
http://dx.doi.org/10.1111/aji.12167
---------- CHICAGO ----------
Hauk, V., Azzam, S., Calo, G., Gallino, L., Paparini, D., Franchi, A., et al. "Vasoactive Intestinal Peptide Induces an Immunosuppressant Microenvironment in the Maternal-Fetal Interface of Non-Obese Diabetic Mice and Improves Early Pregnancy Outcome" . American Journal of Reproductive Immunology 71, no. 2 (2014) : 120-130.
http://dx.doi.org/10.1111/aji.12167
---------- MLA ----------
Hauk, V., Azzam, S., Calo, G., Gallino, L., Paparini, D., Franchi, A., et al. "Vasoactive Intestinal Peptide Induces an Immunosuppressant Microenvironment in the Maternal-Fetal Interface of Non-Obese Diabetic Mice and Improves Early Pregnancy Outcome" . American Journal of Reproductive Immunology, vol. 71, no. 2, 2014, pp. 120-130.
http://dx.doi.org/10.1111/aji.12167
---------- VANCOUVER ----------
Hauk, V., Azzam, S., Calo, G., Gallino, L., Paparini, D., Franchi, A., et al. Vasoactive Intestinal Peptide Induces an Immunosuppressant Microenvironment in the Maternal-Fetal Interface of Non-Obese Diabetic Mice and Improves Early Pregnancy Outcome. Am. J. Reprod. Immunol. 2014;71(2):120-130.
http://dx.doi.org/10.1111/aji.12167