Asian-Australasian Journal of Animal Sciences

Asian Australasian Association of Animal Production Societies (아세아태평양축산학회)
권호 표지
DOI QR코드

DOI QR Code

Effects of IFN-γ on IL-18 Expression in Pregnant Rats and Pregnancy Outcomes

  • Si, Li-Fang (College of Animal Science and Technology, Henan University of Science and Technology) ;
  • Zhang, Shou-Yan (Department of Cardiology, Luoyang Central Hospital Affiliated to Zhengzhou University) ;
  • Gao, Chun-Sheng (College of Animal Science and Veterinary Medicine, Henan Agricultural University) ;
  • Chen, Shu-Lin (College of Veterinary Medicine, Northwest A & F University) ;
  • Zhao, Jin (College of Veterinary Medicine, Northwest A & F University) ;
  • Cheng, Xiang-Chao (College of Animal Science and Technology, Henan University of Science and Technology)
  • Received : 2013.02.12
  • Accepted : 2013.07.10
  • Published : 2013.10.01
Download PDF
⟨ Previous Next ⟩

Abstract

The present study focused on establishing the effects of interferon-gamma (IFN-${\gamma}$) on interleukin-18 (IL-18) expression patterns and pregnancy outcomes in pregnant rats. Pregnant rats at the post-implantation stage were randomized into control, low IFN-${\gamma}$ (L-IFN-${\gamma}$) and high IFN-${\gamma}$ groups (H-IFN-${\gamma}$) that received normal saline, 100 IU/g of IFN-${\gamma}$ and 500 IU/g of IFN-${\gamma}$ vaginal muscular injection, respectively. The effects of IFN-${\gamma}$ on IL-18 expression and pregnancy outcomes were assessed systematically using several methods, including immunohistochemistry streptavidin-perosidase (SP), image pattern analysis, enzyme-linked immune-sorbent assay (ELISA), whole blood count (WBC) count, microscopy and visual observation. IL-18 was detected in the uteri of all pregnant rats, and mainly distributed in the endometrium, decidual cells, vascular endothelium and myometrium. Immunohistochemistry and image pattern analyses revealed significantly lower IL-18 expression in the H-IFN-${\gamma}$ group compared to the L-IFN-${\gamma}$ and control groups (p<0.01), indicating that high doses of IFN-${\gamma}$ induce downregulation of IL-18 in the uterus of pregnant rats. ELISA results disclosed that IL-18 expression in peripheral blood of the H-IFN-${\gamma}$ group was lower than that of the L-IFN-${\gamma}$ group (p<0.05), and significantly reduced compared to the control group (p<0.01). Moreover, the number of peripheral leukocytes in the H-IFN-${\gamma}$ group was significantly higher than those in the control and L-IFN-${\gamma}$ groups (p<0.01). Morphology analysis showed no evident differences between the L-IFN-${\gamma}$ and control groups. However, for the H-IFN-${\gamma}$ group, uterine mucosa bleeding, necrosis and excoriation were observed using microscopy. Visual observation revealed marroon, swelling, crassitude and no embryo in the uterus, which are obvious indicators of abortion. These results indicate that IFN-${\gamma}$ plays a regulatory role in IL-18 expression in the uterus and peripheral blood of pregnant rats at the post-implantation stage. Moreover, high levels (500 IU/g) of IFN-${\gamma}$ influence normal pregnancy at the early stages in rats by downregulating IL-18 expression in the uterus and peripheral blood and increasing the number of peripheral leukocytes, consequently triggering termination of pregnancy.

Keywords

References

  1. Andrea, R., R. D. Wheelerb, and P. D. Collinsa. 2003. Identification of a truncated IL-18Rh mRNA: a putative regulator of IL-18 expressed in rat brain. J. Neuroimmunol. 145:40-45. https://doi.org/10.1016/j.jneuroim.2003.09.005
  2. Ashkar, A. A. and B. A. Croy. 1999. Interferon contributes to the normalcy of murine pregnancy biology of reproduction. J. Biol. Reprod. 61:493-502. https://doi.org/10.1095/biolreprod61.2.493
  3. Cao, Y. Q., D. M. Sun, Y. Z. Chen, and P. D. Zhu. 1999. Studies on the antifertility effect and the mechanism of action of human recombinant interferon-gamma in rabbits. J. Reprod. Med. 8:98-102.
  4. Dosiou, C. and L. C. Giudice. 2005. Natural killer cells in pregnancy and recurrent pregnancy loss: endocrine and immunologic perspectives. J. Endocrine Reviews, 26:44-62. https://doi.org/10.1210/er.2003-0021
  5. Goodbourn, S., L. Didcock, and R. E. Randall. 2000. Interferons:cell signalling, immune modulation, antiviral responses and virus countermeasures. J. Gen. Virol. 81:2341-2364.
  6. Gruber, C. J. and J. C. Huber. 2005. The role of dydrogesterone in recurrent abortion. J. Steroid Biochem. Mol. Biol. 97:426-430. https://doi.org/10.1016/j.jsbmb.2005.08.009
  7. Hu, C. D. and S. Q. Gui. 2004. Expression and significance of HB-EGF in trophoblast of patients with spontaneous abortion. J. Shanghai Med. J. 27:491-494.
  8. Kanno, T., T. Nagata, S. Yamamoto, H. Okamura, and T. Nishizaki. 2004. Interleukin-18 stimulates synaptically released glutamate and enhances postsynaptic AMPA receptor responses in the CA1 region of mouse hippocampal slices. Brain Res. 1012:190-193. https://doi.org/10.1016/j.brainres.2004.03.065
  9. Koibuchi, N., M. Fujita, M. Hashimoto, F. S. Dhabhar, and B. Conti. 2006. The adrenal gland is a source of stress-induced circulating IL-18. J. Neuroimmunol. 172:59-65. https://doi.org/10.1016/j.jneuroim.2005.11.001
  10. Ledee-Bataille, N., F. Olivennes, J. Kadoch, S. Dubanchet, N. Frygdman, G. Chaouat, and R. Frygamn. 2004. Detectable levels of interleukin-18 in uterine luminal secretions at oocyte retrieval predict failure of the embryo transfer. Hum. Reprod. 19:1968-1973. https://doi.org/10.1093/humrep/deh356
  11. Liu, M. L., J. P. Peng, Q. H. Sun,Y. Yang, and H. F. Xia. 2005. The expression of TGF-${\beta}1$ in uterus and placenta of pregnant rat and its regulation by IFN-$\gamma$. Progress in Biochemistry and Biophysics 32:413-420.
  12. Liu, Z., Y. Chen, and J. P. Peng. 2002. The effect on MHC class II expression and apoptosis in placenta by IFN-$\gamma$ administration. Contraception 65:177-184. https://doi.org/10.1016/S0010-7824(01)00277-3
  13. Luo, Q., W. X. Ning, Y. T. Wu, X. M. Zhu, F. Jin, J. Z. Sheng, and H. F. Huang. 2006. Altered expression of interleukin-18 in the ectopic and eutopic endometrium of women with endometriosis. J. Reprod. Immunol. 72:108-117. https://doi.org/10.1016/j.jri.2006.03.003
  14. Madonna, S., C. Scarponi, R. Sestito, S. Pallotta, A. Cavani, and C. Albanesi. 2010. The IFN-$\gamma$-dependent suppressor of cytokine signaling 1 promoter activity is positively regulated by IFN regulatory factor-1 and sp1 but repssed by growth factor Independence-1b and Kruppel-Like factor-4, and it is dysregulated in psoriatic keratinocytes. J. Immunol. 185:2467-2481. https://doi.org/10.4049/jimmunol.1001426
  15. Okamura, H., K. Nagata, T. Komatsu, T. Tanimoto, Y. Nukata, F. Tanabe, K. Akita, K. Torigoe, T. Okura, and S. Fukuda. 1995. A novel costimulatory factor for gamma interferon induction found in the livers of minusc ausesendotoxic shock. Infect. Immun. 63:3966-3972.
  16. Ostojic, S., M. Volk, I. Medica, M. Kapović, H. Meden-Vrtovec, and B. Peterlin. 2007. Polymorphisms in the interleukin-12/18 genes and recurrent spontaneous abortion. Am. J. Reprod. Immunol. 58:403-408. https://doi.org/10.1111/j.1600-0897.2007.00501.x
  17. Sakai, M., A. Shiozaki, Y. Sasaki, S. Yoneda, and S. Saito. 2004. The ratio of interleukin (IL)-18 to IL-12 secreted by peripheral blood mononuclear cells is increased in normal pregnant subjects and decreased in pre-eclamptic patients. J. Reprod. Immunol. 61:133-143. https://doi.org/10.1016/j.jri.2004.01.001
  18. Shan, N. N., X. J. Zhu, J. Peng, P. Qin, X. W. Zhuang, H. C. Wang, and M. Hou. 2009. Interleukin 18 and interleukin 18 binding protein in patients with idiopathic thrombocytopenic Purpura. Br. J. Haematol. 144:755-761. https://doi.org/10.1111/j.1365-2141.2008.07520.x
  19. Shan, N. N., X. J. Zhu, Q. Wang, C. Y. Wang, P. Qin, J. Peng, and M. Hou. 2009. High-dose dexamethasone regulates interlenkin-18 and interleukin-18 binding protein in idiopathic thrombocytopenic purpura. Haematologica 94:1603-1607. https://doi.org/10.3324/haematol.2009.007708
  20. Sugama, S., M. Fujita, M. Hashimoto, and B. Conti. 2007. Stress induced morphological microglial activation in the rodent brain: involvement of interleukin-18. Neuroscience 146:1388-1399. https://doi.org/10.1016/j.neuroscience.2007.02.043
  21. Thomas, H. E., R. Darwiche, J. A. Corbett, and T. W. Kay. 2002. Interleukin-1 plus $\gamma$-interferon-induced pancreatic $\beta$-cell dysfunction is mediate by $\beta$-cell nitric oxide production. Diabetes 51:311-316. https://doi.org/10.2337/diabetes.51.2.311
  22. Wang, N., S. Sugama, B. Conti, A. Teramoto, and T. Shibasaki. 2006. Interleukin-18 mRNA expression in the rat pituitary gland. J. Neuroimmunol. 173:117-125. https://doi.org/10.1016/j.jneuroim.2005.12.009
  23. Xue, J. Z., Y. Y. Cui, T. Zhang, S. Q. Liu, H. Q. Duan, Yang Zuo J, G. Hu, and X. Mu. 2011. IFN-$\gamma$ inducing ICAM-1 and IFN-${\gamma}R{\alpha}$expression in cultured rat intestinal mucosa microvascular endothelial cells. J. Acta Anatomica Sinica 42:622-629.

Cited by

  1. Effects of quercetin on Aroclor 1254-induced expression of CYP450 and cytokines in pregnant rats vol.16, pp.1, 2013, https://doi.org/10.1080/1547691x.2019.1604585
  2. The Role and Function of Regulatory T Cells in Toxoplasma gondii-Induced Adverse Pregnancy Outcomes vol.2021, pp.None, 2013, https://doi.org/10.1155/2021/8782672
  3. Interferon γ neutralization reduces blood pressure, uterine artery resistance index, and placental oxidative stress in placental ischemic rats vol.321, pp.2, 2013, https://doi.org/10.1152/ajpregu.00349.2020