- Narges Abbasi
- - Faculty of Basic Sciences, Science and Research Branch, Islamic Azad University, Tehran, Iran
- Amir Hassan Zarnani
- 1- Nanobiotechnology Research Center, Avicenna Research Institute (ACECR), Tehran, Iran
- 2- Department of Immunology, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran
- Pouneh Dokouhaki
- - Monoclonal Antibody Research Center, Avicenna Research Institute (ACECR), Tehran, Iran
- Jamileh Ghasemi
- - Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECR, Tehran, Iran
- Abdolamir Feyzi
- - Department of Pathology, Faculty of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
- Mohammad Mehdi Akhondi
- - Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECR, Tehran, Iran
- Mahmood Jeddi-Tehrani
 - - Monoclonal Antibody Research Center, Avicenna Research Institute (ACECR), Tehran, Iran
Received: 7/1/2006 Accepted: 7/1/2006 - Publisher : Avicenna Research Institute |
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Abstract
Introduction: Activation of Indolamine 2,3-dioxygenase (IDO), an enzyme responsible for tryptophan catabolism, has been reported to be a necessary requirement to achieve immunological tolerance against the fetus and protection against intracellular and extracellular pathogens. The objective of this study was to evaluate the expression of IDO gene in murine endometrium and its expression rate in different phases of estrous cycle. Noticing the role of this enzyme especially in the survival of a semi-antigenic embryo, the results of this study may be used as a basis for practical studies on the immunologic bases of recurrent abortions.Materials & Methods: In this experimental study, we studied the expression of IDO in the female BALB/c mice endometrium during four stages of estrous cycle .The phases of estrous cycle were determined by examining vaginal cytology .At each phase, endometrium was pealed away and the relative expression of IDO mRNA was detected by semi-quantitative RT-PCR using specific primers to IDO and mGAPDH as a housekeeping gene. The specificity of reaction was confirmed by enzymatic digestion of amplicon which yielded to 138bp and 259bp fragments .Results: Our results showed, for the first time, that IDO is expressed in the endometrium of cycling mice during all stages of estrous cycle. The expression of IDO was highest at estrus and lowest at diestrus (p<.001). Conclusion: Expression of IDO in endometrium during all phases of estrous cycle reveals that this enzyme as an effective arm of innate immune system may serve a role in protecting the female reproductive tract against ascending infections. Also regarding the fact that, mating only occurs at estrus phase, the high expression of IDO in this phase, may act as the main mechanism in inducing immunological tolerance to the fetus.
Keywords:
Indolamine 2,3- dioxygenase, Mice, Endometrium, Estrous cycle, Immunological tolerance, Recurrent abortion To cite this article:References
- Munn D.H., Zhou M., Attwood J.T., Bondarev I., Con-way S.J., Marshall B., et al. Prevention of allogeneic
- Suzuki S., Tone S., Takikawa O., Kubo T., Kohno I., Minatogawa Y. Expression of indoleamine 2,3-dioxy-
- Sedlmayr P., Blaschitz A., Wintersteiger R., Semlitsch M., Hammer A., MacKenzie C.R., et al. Localization of indoleamine 2,3-dioxygenase in human female reproductive organs and the placenta. Mol Hum Reprod. 2002;8(4):385-91
- Kudo Y., Boyd C.A. Human placental indoleamine 2,3-dioxygenase: cellular localization and characterization of an enzyme preventing fetal rejection. Biochim Biophys Acta. 2000;1500(1):119-24
- Taylor M.W., Feng G.S. Relationship between inter-feron-gamma, indoleamine 2,3-dioxygenase, and tryptophan catabolism. FASEB J. 1991;5(11):2516-22. Review
- Mellor A.L., Munn D.H. Extinguishing maternal immune responses during pregnancy: implications for immunosuppressionSemin Immunol.2001;13(4):213-8
- Frumento G., Rotondo R., Tonetti M., Ferrara G.B. T cell proliferation is blocked by indoleamine 2,3-dioxygenase. Transplant Proc. 2001;33(1-2):428-30
- Takikawa O., Habara-Ohkubo A., Yoshida R. IFN-gamma is the inducer of indoleamine 2,3-dioxygenase in allografted tumor cells undergoing rejection. J Immunol. 1990;145(4):1246-50
- Werner-Felmayer G., Werner E.R., Fuchs D., Hausen A., Reibnegger G., Wachter H. Characteristics of inter-feron induced tryptophan metabolism in human cells in vitro. Biochim Biophys Acta. 1989;1012 (2):140-7
- Fuchs D., Malkovsky M., Reibnegger G., Werner E.R., Forni G., Wachter H. Endogenous release of interferon gamma and diminished response of peripheral blood mononuclear cells to antigenic stimulation. Immunol Lett. 1989;23(2):103-8. Review
- Munn D.H., Shafizadeh E., Attwood J.T., Bondarev I., Pashine A., Mellor A.L. Inhibition of T cell prolifera-tion by macrophage tryptophan catabolism.J Exp Med. 1999;189(9):1363-72
- Hwu P., Du M.X., Lapointe R., Do M., Taylor M.W., Young H.A. Indoleamine 2,3-dioxygenase production by human dendritic cells results in the inhibition of T cell proliferation. J Immunol. 2000; 164(7):3596-9
- Fallarino F., Vacca C., Orabona C., Belladonna M.L., Bianchi R., Marshall B., et al. Functional expression of indoleamine 2,3-dioxygenase by murine CD8 alpha (+) dendritic cells. Int Immunol. 2002;14(1):65-8
- Yoshida R., Urade Y., Nakata K., Watanabe Y., Haya-ishi O. Specific induction of indoleamine 2,3-dioxy-genase by bacterial lipopolysaccharide in the mouse lung. Arch Biochem Biophys. 1981;212(2):629-37
- Malina H.Z., Martin X.D. Indoleamine 2,3-dioxy-genase: antioxidant enzyme in the human eye. Graefes Arch Clin Exp Ophthalmol. 1996;234(7):457-62
- Yamazaki F., Kuroiwa T., Takikawa O., Kido R. Human indolylamine 2,3-dioxygenase. Its tissue distri-bution, and characterization of the placental enzyme. Biochem J. 1985;230(3):635-8
- Zarnani A.H., Moazzeni S.M., Shokri F., Salehnia M., Dokouhaki P., Shojaeian J., et al. The efficient isola-tion of murine splenic dendritic cells and their cyto-chemical features. Histochem Cell Biol. 2006;126(2): 275-82
- Thellin O., Heinen E. Pregnancy and the immune system: between tolerance and rejection. Toxicology. 2003;185(3):179-84. Review
- مصفا نريمان، زرناني امير حسن، حسن زهير محمد. ايمونولوزي حاملگي طبيعي. چاپ اول، دانشگاه علوم پزشکي و خدمات بهداشتيـ درماني شهيد بهشتي (1382)، فصل 6، صفحات: 181-164
- Heyborne K., Silver R.M. Immunology of postim-plantation pregnancy, In: Reproductive Immunolog, Bronson R. (Editors), Blakwell scientific publitions Ltd. 1996;pp:383-417
- Mellor A.L., Munn D.H. Tryptophan catabolism pre-vents maternal T cells from activating lethal anti-fetal immune responses. J Reprod Immunol. 2001;52(1-2): 5-13. Review
- Hunt J.S., Robertson S.A. Uterine macrophages and environmental programming for pregnancy success. J Reprod Immunol. 1996;32(1):1-25. Review
- Mellor A.L., Sivakumar J., Chandler P., Smith K., Molina H., Mao D., et al. Prevention of T cell-driven complement activation and inflammation by trypto-phan catabolism during pregnancy. Nat Immunol. 2001;2(1):64-8
- Zarnani A.H., Dokouhaki P., Tehrani M.J., Indole-amine 2,3-Dioxygenase and Immunological Tolerance during Pregnancy. Iranian J Immunol. 2004;1:143-153. Rewiew
- مصفا نريمان، زرناني امير حسن، حسن زهير محمد، ايمونولوژي حاملگي طبيعي. چاپ اول، دانشگاه علوم پزشكي و خدمات بهداشتيـ درماني شهيد بهشتي (1382)، فصل 5، صفحات: 156-135
- Zarnani A.H., Moazzeni S.M., Shokri F., Salehnia M., Dokouhaki P., Shojaeian J., et al. Analysis of endo-metrial myeloid and lymphoid dendritic cells during mouse estrus cycle. J Reprod Immunol. 2006;71(1):28-40
- Erlebacher A. Why isn't the fetus rejected? Curr Opin Immunol. 2001;13(5):590-3.