한국수정란이식학회지 (Journal of Embryo Transfer)

  • 제31권4호
  • /
  • Pages.323-333
  • /
  • 2016
  • /
  • 2508-755X(pISSN)
  • /
  • 2288-0178(eISSN)
한국수정란이식학회 (The Korean Society of Embryo Transfer)
권호 표지
DOI QR코드

DOI QR Code

Pro-inflammatory Cytokines and Their Receptors: Expression and Regulation in the Uterine Endometrium during the Estrous Cycle in Pigs

  • Yoo, Inkyu (Department of Biological Science and Technology, Yonsei University) ;
  • Kim, Minjeong (Department of Biological Science and Technology, Yonsei University) ;
  • Han, Jisoo (Department of Biological Science and Technology, Yonsei University) ;
  • Jang, Hwanhee (Department of Biological Science and Technology, Yonsei University) ;
  • Choi, Sun-Ho (Swine Science Division, National Institute of Animal Science, Rural Development Administration) ;
  • Ka, Hakhyun (Department of Biological Science and Technology, Yonsei University)
  • 투고 : 2016.11.30
  • 심사 : 2016.12.28
  • 발행 : 2016.12.31
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

Pro-inflammatory cytokines, interleukin-$1{\beta}$(IL1B), IL6, and tumor necrosis factor-alpha (TNF), are known to play important roles in regulating the endometrial function in the uterus during the estrous cycle and pregnancy in several species. However, the expression and function of these cytokines and their receptors in the uterine endometrium during the estrous cycle have not been studied in pigs. Thus, this study determined the expression and regulation of IL1B, IL6, TNF and their respective receptors, IL1R1, IL1RAP, IL6R, GP130, TNFRSF1A, and TNFRSF1B during the estrous cycle in pigs. To analyze levels of each gene expression in the uterine endometrium we obtained from endometrial tissues on Days 0, 3, 6, 9, 12, 15, and 18 of the estrous cycle. Real-time RT-PCR analysis showed that levels of IL1B, IL1RAP, IL6R, GP130, TNF, TNFRSF1A, and TNFRSF1B mRNAs were highest on Day 15 or 18 of the estrous cycle, which corresponds to the proestrus period. Levels of IL1R1 were highest on Day 0, while levels of IL6 were biphasic with high levels on Day 6 and Day 15. The abundance of IL1B, IL6, IL6R, and TNF mRNAs was decreased by progesterone, while levels of GP130 were increased by progesterone in endometrial tissue explants. These results showed that expression of pro-inflammatory cytokines and their receptors changed stage-specifically during the estrous cycle and regulated by progesterone in the uterine endometrium in pigs, suggesting that these pro-inflammatory cytokines may be involved in the regulation endometrial function during the estrous cycle in pigs.

키워드

참고문헌

  1. Anegon I, Cuturi MC, Godard A, Moreau M, Terqui M, Martinat-Botte F and Soulillou JP. 1994. Presence of leukaemia inhibitory factor and interleukin 6 in porcine uterine secretions prior to conceptus attachment. Cytokine 6(5):493-499. https://doi.org/10.1016/1043-4666(94)90076-0
  2. Blitek A, Morawska E and Ziecik AJ. 2012. Regulation of expression and role of leukemia inhibitory factor and interleukin-6 in the uterus of early pregnant pigs. Theriogenology 78(5):951-964. https://doi.org/10.1016/j.theriogenology.2012.05.016
  3. Chen HL, Yang YP, Hu XL, Yelavarthi KK, Fishback JL and Hunt JS. 1991. Tumor necrosis factor alpha mRNA and protein are present in human placental and uterine cells at early and late stages of gestation. Am. J. Pathol. 139(2): 327-335.
  4. Choudhuri R and Wood GW. 1993. Production of interleukin-1, interleukin-6, and tumor necrosis factor alpha in the uterus of pseudopregnant mice. Biol. Reprod. 49(3):596-603. https://doi.org/10.1095/biolreprod49.3.596
  5. Clark AR and Kruger JA. 2016. Mathematical modeling of the female reproductive system: from oocyte to delivery. Wiley Interdiscip. Rev. Syst. Biol. Med.
  6. Correia-Alvarez E, Gomez E, Martin D, Carrocera S, Perez S, Peynot N, Giraud-Delville C, Caamano JN, Balseiro A, Sandra O, Duranthon V and Munoz M. 2015. Early embryonic and endometrial regulation of tumor necrosis factor and tumor necrosis factor receptor 2 in the cattle uterus. Theriogenology 83(6):1028-1037. https://doi.org/10.1016/j.theriogenology.2014.12.007
  7. De M, Sanford TH and Wood GW. 1992. Detection of Interleukin-1, Interleukin-6, and Tumor-Necrosis-Factor-Alpha in the Uterus during the 2nd-Half of Pregnancy in the Mouse. Endocrinology 131(1):14-20. https://doi.org/10.1210/endo.131.1.1611993
  8. Diehl S and Rincon M. 2002. The two faces of IL-6 on Th1/Th2 differentiation. Mol. Immunol. 39(9):531-536. https://doi.org/10.1016/S0161-5890(02)00210-9
  9. Franczak A, Wojciechowicz B, Zmijewska A, Kolakowska J and Kotwica G. 2013. The effect of interleukin 1beta and interleukin 6 on estradiol-17beta secretion in the endometrium of pig during early pregnancy and the estrous cycle. Theriogenology 80(2):90-98. https://doi.org/10.1016/j.theriogenology.2013.03.020
  10. Franczak A, Zmijewska A, Kurowicka B, Wojciechowicz B, Petroff BK and Kotwica G. 2012. The effect of tumor necrosis factor alpha (TNFalpha), interleukin 1beta (IL1beta) and interleukin 6 (IL6) on endometrial PGF2alpha synthesis, metabolism and release in early-pregnant pigs. Theriogenology 77(1):155-165. https://doi.org/10.1016/j.theriogenology.2011.07.029
  11. Fumuso E, Giguere S, Wade J, Rogan D, Videla-Dorna I and Bowden RA. 2003. Endometrial IL-1beta, IL-6 and TNF-alpha, mRNA expression in mares resistant or susceptible to post-breeding endometritis. Effects of estrous cycle, artificial insemination and immunomodulation. Vet. Immunol. Immunopathol. 96(1-2):31-41. https://doi.org/10.1016/S0165-2427(03)00137-5
  12. Gray CA, Bartol FF, Tarleton BJ, Wiley AA, Johnson GA, Bazer FW and Spencer TE. 2001. Developmental biology of uterine glands. Biol. Reprod. 65(5):1311-1323. https://doi.org/10.1095/biolreprod65.5.1311
  13. Haider S and Knofler M. 2009. Human tumour necrosis factor: physiological and pathological roles in placenta and endometrium. Placenta 30(2):111-123. https://doi.org/10.1016/j.placenta.2008.10.012
  14. Healy LL, Cronin JG and Sheldon IM. 2015. Polarized Epithelial Cells Secrete Interleukin 6 Apically in the Bovine Endometrium. Biol. Reprod. 92(6):151. https://doi.org/10.1095/biolreprod.115.127936
  15. Hirano T, Akira S, Taga T and Kishimoto T. 1990. Biological and clinical aspects of interleukin 6. Immunol. Today 11(12):443-449. https://doi.org/10.1016/0167-5699(90)90173-7
  16. Hondo E, Kokubu K, Kato K and Kiso Y. 2005. Localization of interieukin-6 receptor rnRNA in the pregnant and non-pregnant mouse uterus. J. Reprod. Develop. 51(6):777-781. https://doi.org/10.1262/jrd.17042
  17. Hunt JS, Chen HL, Hu XL and Tabibzadeh S. 1992. Tumor necrosis factor-alpha messenger ribonucleic acid and protein in human endometrium. Biol. Reprod. 47(1):141-147. https://doi.org/10.1095/biolreprod47.1.141
  18. Hunt JS, Miller L, Roby KF, Huang J, Platt JS and DeBrot BL. 1997. Female steroid hormones regulate production of pro-inflammatory molecules in uterine leukocytes. J. Reprod. Immunol. 35(2):87-99. https://doi.org/10.1016/S0165-0378(97)00060-0
  19. Hunter CA and Jones SA. 2015. IL-6 as a keystone cytokine in health and disease. Nat. Immunol. 16(5):448-457. https://doi.org/10.1038/ni.3153
  20. Jacobs AL, Sehgal PB, Julian J and Carson DD. 1992. Secretion and hormonal regulation of interleukin-6 production by mouse uterine stromal and polarized epithelial cells cultured in vitro. Endocrinology 131(3):1037-1046. https://doi.org/10.1210/endo.131.3.1505448
  21. Jana B, Kozlowska A, Andronowska A and Jedlinska-Krakowska M. 2008. The effect of tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1 beta and IL-6 on chorioamnion secretion of prostaglandins (PG)F 2 alpha and E2 in pigs. Reprod. Biol. 8(1):57-68. https://doi.org/10.1016/S1642-431X(12)60004-7
  22. Ka H, Jaeger LA, Johnson GA, Spencer TE and Bazer FW. 2001. Keratinocyte growth factor is up-regulated by estrogen in the porcine uterine endometrium and functions in trophectoderm cell proliferation and differentiation. Endocrinology 142(6):2303-2310. https://doi.org/10.1210/endo.142.6.8194
  23. Kaeoket K, Persson E and Dalin AM. 2002. Corrigendum to "The sow endometrium at different stages of the oestrus cycle: studies on morphological changes and infiltration by cells of the immune system." [Anim. Reprod. Sci. 65 (2001) 95-114]. Anim. Reprod. Sci. 73(1-2):89-107. https://doi.org/10.1016/S0378-4320(02)00126-4
  24. Kelly RW. 2002. Inflammatory mediators and cervical ripening. J. Reprod. Immunol. 57(1-2):217-224. https://doi.org/10.1016/S0165-0378(02)00007-4
  25. Laird SM, Tuckerman EM, Cork BA and Li TC. 2000. Expression of nuclear factor kappa B in human endometrium; role in the control of interleukin 6 and leukaemia inhibitory factor production. Mol. Hum. Reprod. 6(1):34-40. https://doi.org/10.1093/molehr/6.1.34
  26. Lim KJ, Odukoya OA, Ajjan RA, Li TC, Weetman AP and Cooke ID. 1998. Profile of cytokine mRNA expression in peri-implantation human endometrium. Mol. Hum. Reprod. 4(1):77-81. https://doi.org/10.1093/molehr/4.1.77
  27. Livak KJ and Schmittgen TD. 2001. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 25(4):402-408. https://doi.org/10.1006/meth.2001.1262
  28. Mathew DJ, Newsom EM, Guyton JM, Tuggle CK, Geisert RD and Lucy MC. 2015. Activation of the transcription factor nuclear factor-kappa B in uterine luminal epithelial cells by interleukin 1 Beta 2: a novel interleukin 1 expressed by the elongating pig conceptus. Biol. Reprod. 92(4):107. https://doi.org/10.1095/biolreprod.114.126128
  29. Mathialagan N, Bixby JA and Roberts RM. 1992. Expression of interleukin-6 in porcine, ovine, and bovine preimplantation conceptuses. Mol. Reprod. Dev. 32(4):324-330. https://doi.org/10.1002/mrd.1080320404
  30. Modric T, Kowalski AA, Green ML, Simmen RC and Simmen FA. 2000. Pregnancy-dependent expression of leukaemia inhibitory factor (LIF), LIF receptor-beta and interleukin-6 (IL-6) messenger ribonucleic acids in the porcine female reproductive tract. Placenta 21(4):345-353. https://doi.org/10.1053/plac.1999.0493
  31. Palm F, Walter I, Budik S, Kolodziejek J, Nowotny N and Aurich C. 2008. Influence of different semen extenders and seminal plasma on PMN migration and on expression of IL-1beta, IL-6, TNF-alpha and COX-2 mRNA in the equine endometrium. Theriogenology 70(5):843-851. https://doi.org/10.1016/j.theriogenology.2008.04.054
  32. Prins JR, Gomez-Lopez N and Robertson SA. 2012. Interleukin-6 in pregnancy and gestational disorders. J. Reprod. Immunol. 95(1-2):1-14. https://doi.org/10.1016/j.jri.2012.05.004
  33. Robertson SA and Seamark RF. 1990. Granulocyte macrophage colony stimulating factor (GM-CSF) in the murine reproductive tract: stimulation by seminal factors. Reprod. Fertil. Dev. 2(4):359-368. https://doi.org/10.1071/RD9900359
  34. Robertson SA, Mayrhofer G and Seamark RF. 1992. Uterine Epithelial-Cells Synthesize Granulocyte-Macrophage Colony-Stimulating Factor and Interleukin-6 in Pregnant and Nonpregnant Mice. Biol. Reprod. 46(6):1069-1079. https://doi.org/10.1095/biolreprod46.6.1069
  35. Robertson SA, Christiaens I, Dorian CL, Zaragoza DB, Care AS, Banks AM and Olson DM. 2010. Interleukin-6 is an essential determinant of on-time parturition in the mouse. Endocrinology 151(8):3996-4006. https://doi.org/10.1210/en.2010-0063
  36. Roby KF and Hunt JS. 1994. Mouse endometrial tumor necrosis factor-alpha messenger ribonucleic acid and protein: localization and regulation by estradiol and progesterone. Endocrinology 135(6):2780-2789. https://doi.org/10.1210/endo.135.6.7988471
  37. Ross JW, Malayer JR, Ritchey JW and Geisert RD. 2003. Characterization of the interleukin-1beta system during porcine trophoblastic elongation and early placental attachment. Biol. Reprod. 69(4):1251-1259. https://doi.org/10.1095/biolreprod.103.015842
  38. Sanford TR, De M and Wood GW. 1992. Expression of colony-stimulating factors and inflammatory cytokines in the uterus of CD1 mice during days 1 to 3 of pregnancy. J. Reprod. Fertil. 94(1):213-220. https://doi.org/10.1530/jrf.0.0940213
  39. Seo H, Choi Y, Shim J, Choi Y and Ka H. 2012. Regulatory mechanism for expression of IL1B receptors in the uterine endometrium and effects of IL1B on prostaglandin synthetic enzymes during the implantation period in pigs. Biol. Reprod. 87(2):31. https://doi.org/10.1093/biolreprod/87.s1.31
  40. Seo H, Choi Y, Shim J, Yoo I and Ka H. 2014. Comprehensive analysis of prostaglandin metabolic enzyme expression during pregnancy and the characterization of AKR1B1 as a prostaglandin F synthase at the maternal-conceptus interface in pigs. Biol. Reprod. 90(5):99. https://doi.org/10.1095/biolreprod.113.114926
  41. Simon C, Gimeno MJ, Mercader A, O'Connor JE, Remohi J, Polan ML and Pellicer A. 1997. Embryonic regulation of integrins beta 3, alpha 4, and alpha 1 in human endometrial epithelial cells in vitro. J. Clin. Endocrinol. Metab. 82(8):2607-2616. https://doi.org/10.1210/jc.82.8.2607
  42. Simon C, Valbuena D, Krussel J, Bernal A, Murphy CR, Shaw T, Pellicer A and Polan ML. 1998. Interleukin-1 receptor antagonist prevents embryonic implantation by a direct effect on the endometrial epithelium. Fertil. Steril. 70(5):896-906. https://doi.org/10.1016/S0015-0282(98)00275-1
  43. Soede NM, Langendijk P and Kemp B. 2011. Reproductive cycles in pigs. Anim. Reprod. Sci. 124(3-4):251-258. https://doi.org/10.1016/j.anireprosci.2011.02.025
  44. Spencer TE, Wiley AA and Bartol FF. 1993. Neonatal age and period of estrogen exposure affect porcine uterine growth, morphogenesis, and protein synthesis. Biol. Reprod. 48(4):741-751. https://doi.org/10.1095/biolreprod48.4.741
  45. Subramaniam S, Stansberg C and Cunningham C. 2004. The interleukin 1 receptor family. Dev. Comp. Immunol. 28(5):415-428. https://doi.org/10.1016/j.dci.2003.09.016
  46. Tabibzadeh S, Kong QF, Babaknia A and May LT. 1995. Progressive rise in the expression of interleukin-6 in human endometrium during menstrual cycle is initiated during the implantation window. Hum. Reprod. 10(10):2793-2799. https://doi.org/10.1093/oxfordjournals.humrep.a135793
  47. Tarleton BJ, Wiley AA and Bartol FF. 1999. Endometrial development and adenogenesis in the neonatal pig: effects of estradiol valerate and the antiestrogen ICI 182,780. Biol. Reprod. 61(1):253-263. https://doi.org/10.1095/biolreprod61.1.253
  48. Woodward EM, Christoffersen M, Campos J, Betancourt A, Horohov D, Scoggin KE, Squires EL and Troedsson MH. 2013. Endometrial inflammatory markers of the early immune response in mares susceptible or resistant to persistent breeding-induced endometritis. Reproduction 145(3):289-296. https://doi.org/10.1530/REP-12-0452
  49. Yelavarthi KK, Chen HL, Yang YP, Cowley BD, Jr., Fishback JL and Hunt JS. 1991. Tumor necrosis factor-alpha mRNA and protein in rat uterine and placental cells. J. Immunol. 146(11):3840-3848.
  50. Zhao H, Kalish F, Schulz S, Yang Y, Wong RJ and Stevenson DK. 2015. Unique roles of infiltrating myeloid cells in the murine uterus during early to midpregnancy. J. Immunol. 194(8):3713-3722. https://doi.org/10.4049/jimmunol.1401930