{"paper_id":"bf18a883-2c87-4279-914c-cf7687a322ff","body_text":"Abstract\nUsing a murine model, we evaluated the growth of ectopic endometrial tissue in the presence of T helper 1 (Th1) or Th2 cytokines or a nitric oxide donor (S-nitroso-N-acetyl-penicillamine [SNAP]). Female mice were autografted with endometrial tissue in the peritoneum. Different combinations and concentrations of cytokines or SNAP were injected intraperitoneally for 8 weeks. Implants were recovered, measured, and weighed. Cytokines were determined in plasma. Implants (weight and area) were smaller in mice that received interferon γ plus interleukin 2 (IFN-γ + IL-2) compared to mice treated with IL-2, IL-4 + IL-10 or saline solution, and saline solution compared to different concentrations of SNAP. The IL-2, IFN-γ, and IL-4 concentrations in plasma decreased in accordance with the increase in SNAP concentrations compared to saline solution. The promotion of a Th1 milieu in the peritoneum reduced the weight and area of the implant. Different concentrations of SNAP suppressed Th1 and Th2 cytokines and enabled the growth of the implant in this murine model.\nSimilar content being viewed by others\nReferences\nKnapp VJ. How old is endometriosis?. Late 17th- and 18th-century European descriptions of the disease. Fertil Steril. 1999;72(1):10–14.\nFarquhar CM. Extracts from the “clinical evidence”. Endometriosis. BMJ. 2000;320(7247):1449–1452.\nHalme J, Hammond MG, Hulka JF, Raj SG, Talbert LM. Retrograde menstruation in healthy women and in patients with endometriosis. Obstet Gynecol. 1984;64(2):151–154.\nBerkkanoglu M, Arici A. Immunology and endometriosis. Am J Reprod Immunol. 2003;50(1):48–59.\nMier-Cabrera J, Jimenez-Zamudio L, Garcia-Latorre E, Cruz-Orozco O, Hernandez-Guerrero C. Quantitative and qualitative peritoneal immune profiles, T-cell apoptosis and oxidative stress-associated characteristics in women with minimal and mild endometriosis. BJOG. 2011;118(1):6–16.\nOsuga Y, Koga K, Hirota Y, Hirata T, Yoshino O, Taketani Y. Lymphocytes in endometriosis. Am J Reprod Immunol. 2011;65(1):1–10.\nSikora J, Mielczarek-Palacz A, Kondera-Anasz Z. Role of natural killer cell activity in the pathogenesis of endometriosis. Curr Med Chem. 2011;18(2):200–208.\nQuaranta MG, Porpora MG, Mattioli B, et al. Impaired NK-cell-mediated cytotoxic activity and cytokine production in patients with endometriosis: a possible role for PCBs and DDE. Life Sci. 2006;79(5):491–498.\nWu MY, Ho HN. The role of cytokines in endometriosis. Am J Reprod Immunol. 2003;49(5):285–296.\nHo HN, Wu MY, Yang YS. Peritoneal cellular immunity and endometriosis. Am J Reprod Immunol. 1997;38(6):400–412.\nDrosdzol-Cop A, Skrzypulec-Plinta V, Stojko R. Serum and peritoneal fluid immunological markers in adolescent girls with chronic pelvic pain. Obstet Gynecol Surv. 2012;67(6):374–381.\nGringhuis SI, Leow A, Papendrecht-Van Der Voort EA, Remans PH, Breedveld FC, Verweij CL. Displacement of linker for activation of T cells from the plasma membrane due to redox balance alterations results in hyporesponsiveness of synovial fluid T lymphocytes in rheumatoid arthritis. J Immunol. 2000;164(4):2170–2179.\nCemerski S, Cantagrel A, Van Meerwijk JP, Romagnoli P. Reactive oxygen species differentially affect T cell receptor-signaling pathways. J Biol Chem. 2002;277(22):19585–19593.\nMurata Y, Shimamura T, Hamuro J. The polarization of T(h)l/ T(h)2 balance is dependent on the intracellular thiol redox status of macrophages due to the distinctive cytokine production. Int Immunol. 2002;14(2):201–212.\nCarvalho LF, Samadder AN, Agarwal A, Fernandes LF, Abrao MS. Oxidative stress biomarkers in patients with endometriosis: systematic review. Arch Gynecol Obstet. 2012;286(4):1033–1040.\nLousse JC, Van Langendonckt A, Defrere S, Ramos RG, Colette S, Donnez J. Peritoneal endometriosis is an inflammatory disease. Front Biosci (Elite Ed). 2012;4:23–40.\nChang RH, Feng MH, Liu WH, Lai MZ. Nitric oxide increased interleukin-4 expression in T lymphocytes. Immunology. 1997;90(3):364–369.\nKidd P. Th1/Th2 balance: the hypothesis, its limitations, and implications for health and disease. Altern Med Rev. 2003;8(3):223–246.\nSecretaría de Agriculture G, Rural Desarrollo, Alimentatión Pesca y. In: Secretaría de Agricultura G, Rural Desarrollo, Alimentatión Pesca y, eds. Especificaciones técnicas para la producción, cuidado y uso de los animales de laboratorio. Vol. 062-ZOO. México: Diario Oficial de la Federatión; 1999:58.\nDalal SJ, Estep JS, Valentin-Bon IE, Jerse AE. Standardization of the Whitten Effect to induce susceptibility to Neisseria gonorrhoeae in female mice. Contemp Top lab Anim Sci. 2001;40(2):13–17.\nPallares P, Gonzalez-Bulnes A. A new method for induction and synchronization of oestrus and fertile ovulations in mice by using exogenous hormones. Lab Anim. 2009;43(3):295–299.\nBradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein–dye binding. Anal Biochem. 1976;72:248–254.\nBarrier BF. Immunology of endometriosis. Clin Obstet Gynecol. 2010;53(2):397–402.\nLebovic DI, Mueller MD, Taylor RN. Immunobiology of endometriosis. Fertil Steril. 2001;75(1):1–10.\nSomigliana E, Vigano P, Rossi G, Carinelli S, Vignali M, Panina-Bordignon P. Endometrial ability to implant in ectopic sites can be prevented by interleukin-12 in a murine model of endometriosis. Hum Reprod. 1999;14(12):2944–2950.\nItoh H, Sashihara T, Hosono A, Kaminogawa S, Uchida M. Interleukin-12 inhibits development of ectopic endometriotic tissues in peritoneal cavity via activation of NK cells in a murine endometriosis model. Cytotechnology. 2011;63(2):133–141.\nVan Langendonckt A, Casanas-Roux F, Donnez J. Oxidative stress and peritoneal endometriosis. Fertil Steril. 2002;77(5):861–870.\nSzczepanska M, Kozlik J, Skrzypczak J, Mikolajczyk M. Oxidative stress may be a piece in the endometriosis puzzle. Fertil Steril. 2003;79(6):1288–1293.\nJohnson MC, Maliqueo M, Boric MA, Villavicencio A, Vantman D, Vega M. Differential in vitro actions of nitric oxide on human endometrial cell survival. Fertil Steril. 2004;81(1):176–184.\nThomas DD, Ridnour LA, Isenberg JS, et al. The chemical biology of nitric oxide: implications in cellular signaling. Free Radic Biol Med. 2008;45(1):18–31.\nvan der Veen RC, Dietlin TA, Pen L, Gray JD. Nitric oxide inhibits the proliferation of T-helper 1 and 2 lymphocytes without reduction in cytokine secretion. Cell Immunol. 1999; 193(2):194–201.\nNiedbala W, Wei XQ, Campbell C, Thomson D, Komai-Koma M, Liew FY. Nitric oxide preferentially induces type 1 T cell differentiation by selectively up-regulating IL-12 receptor beta 2 expression via cGMP. Proc Natl Acad Sci USA. 2002;99(25):16186–16191.\nNiedbala W, Cai B, Liew FY. Role of nitric oxide in the regulation of T cell functions. Ann Rheum Dis. 2006;65(suppl 3):iii37–iii40.\nNgo C, Chereau C, Nicco C, Weill B, Chapron C, Batteux F. Reactive oxygen species controls endometriosis progression. Am J Pathol. 2009;175(1):225–234.\nVillalobo A. Nitric oxide and cell proliferation. FEBS J. 2006;273(11):2329–2344.\nNiedbala W, Cai B, Liu H, Pitman N, Chang L, Liew FY. Nitric oxide induces CD4+CD25+ Foxp3 regulatory T cells from CD4+CD25 T cells via p53, IL-2, and OX40. Proc Natl Acad Sci USA. 2007;104(39):15478–15483.\nAuthor information\nAuthors and Affiliations\nCorresponding author\nRights and permissions\nAbout this article\nCite this article\nMier-Cabrera, J., González-Gallardo, S. & Hernández-Guerrero, C. Effect of Nitric Oxide and Th1/Th2 Cytokine Supplementation Over Ectopic Endometrial Tissue Growth in a Murine Model of Endometriosis. Reprod. Sci. 20, 1332–1338 (2013). https://doi.org/10.1177/1933719113485297\nPublished:\nIssue date:\nDOI: https://doi.org/10.1177/1933719113485297","source_license":"CC0","license_restricted":false}