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Home / Equine Research Bank / Am J Reprod Immunol / Evaluating the IL-6 Family of Cytokines Throughout Equine Ge...
American journal of reproductive immunology (New York, N.Y. : 1989)2024; 92(1); e13910; doi: 10.1111/aji.13910

Evaluating the IL-6 Family of Cytokines Throughout Equine Gestation.

Abstract: The interleukin (IL)-6 family of cytokines is grouped by a common receptor subunit (gp130), but functions in distinct but overlapping physiological activities, including regulation of acute phase reaction and the balance between effector and regulatory T cell populations-both of which play a role in successful pregnancy maturation. Methods: Here, we aim to assess the expression profiles of members of the IL-6 cytokine family throughout equine gestation. To do so, RNA Sequencing was performed on chorioallantois and endometrium of mares at 120, 180, 300, and 330 days of gestation (n = 4/stage), as well as 45-day chorioallantois (n = 4) and diestrus endometrium (n = 3). Expression levels of members of the IL-6 cytokine family including ciliary neurotrophic factor (CNTF), cardiotrophin 1 (CT-1), cardiotrophin-like cytokine factor 1 (CLCF1), galectin-10, oncostatin M (OSM), and IL-6, -11, and -27 were evaluated in addition to the receptors for IL-6 (IL-6R) and the common receptor subunit gp130. Additionally, peripheral concentration of IL-6 was assessed. Results: In the chorioallantois, differential expression of IL-6, IL-11, CNTF, CLCF1, OSM, and CT-1 was noted. In the endometrium, the gestational age of pregnancy impacted the expression of IL-11, CNTF, and CT-1. Circulatory IL-6 concentrations reached their highest concentrations at 120 days, with lesser concentrations noted at 45, 180, 300, and 330 days. Both IL-6R and gp130 altered in expression throughout equine gestation. Conclusions: In conclusion, members of the IL-6 cytokine family appear to fluctuate constantly throughout equine pregnancy, with varying expression profiles noted when comparing individual members. Additionally, different expression profiles were noted when comparing chorioallantois, endometrium, and circulation, indicating that the function of the cytokine is tissue-specific.
© 2024 The Author(s). American Journal of Reproductive Immunology published by John Wiley & Sons Ltd.
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Publication Date: 2024-07-29 PubMed ID: 39072818DOI: 10.1111/aji.13910Google Scholar: Lookup
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  • Journal Article

Summary

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The research paper discusses the study conducted on the expression profiles of the IL-6 cytokine family throughout equine gestation. The researched noted that different members of the IL-6 cytokine family fluctuated throughout the equine pregnancy, and varied in expression when comparing individual cytokines and when comparing different tissues.

Objective of the Research

  • The main objective of the research was to assess the expression profiles of the interleukin (IL)-6 family of cytokines throughout the gestation period in horses. This family includes ciliary neurotrophic factor (CNTF), cardiotrophin 1 (CT-1), cardiotrophin-like cytokine factor 1 (CLCF1), galectin-10, oncostatin M (OSM), and IL-6, -11, and -27. The study also aimed to measure the levels of IL-6 in the blood throughout the gestation period.

Methods Used

  • To achieve this objective, the researchers performed RNA Sequencing on chorioallantois and endometrium of mares at various stages of gestation, specifically at 120, 180, 300, and 330 days of gestation. The same procedure was done on 45-day chorioallantois and diestrus endometrium.
  • They then evaluated the expression levels of members of the IL-6 cytokine family mentioned above, along with the receptors for IL-6 (IL-6R) and the common receptor subunit gp130.

Results

  • The researchers found differential expressions of IL-6, IL-11, CNTF, CLCF1, OSM, and CT-1 in the chorioallantois. Similarly, they noted that the gestational age impacted the expression of IL-11, CNTF, and CT-1 in the endometrium.
  • On measuring the concentration of IL-6 in the blood, the team found that the levels peaked at 120 days of gestation, and were lesser at other days of gestation.
  • They also found that both IL-6R and gp130 altered in their expression throughout the gestation period in horses.

Conclusions

  • The researchers concluded that members of the IL-6 cytokine family are constantly fluctuating throughout horse pregnancy. This fluctuation was found to vary not only among the different members of the family but also when comparing different tissues where the cytokine functions.

Cite This Article

APA
Fedorka CE, Scoggin KE, El-Sheikh Ali H, Troedsson MHT. (2024). Evaluating the IL-6 Family of Cytokines Throughout Equine Gestation. Am J Reprod Immunol, 92(1), e13910. https://doi.org/10.1111/aji.13910

Publication

American journal of reproductive immunology (New York, N.Y. : 1989)
ISSN: 1600-0897
NlmUniqueID: 8912860
Country: Denmark
Language: English
Volume: 92
Issue: 1
Pages: e13910

Researcher Affiliations

Fedorka, Carleigh E
  • Department of Animal Sciences, Colorado State University, Fort Collins, Colorado, USA.
Scoggin, Kirsten E
  • Department of Veterinary Sciences, University of Kentucky, Lexington, Kentucky, USA.
El-Sheikh Ali, Hossam
  • Department of Veterinary Sciences, University of Kentucky, Lexington, Kentucky, USA.
Troedsson, Mats H T
  • Department of Veterinary Sciences, University of Kentucky, Lexington, Kentucky, USA.

MeSH Terms

  • Animals
  • Horses / immunology
  • Female
  • Pregnancy
  • Interleukin-6 / metabolism
  • Cytokines / metabolism
  • Endometrium / metabolism
  • Endometrium / immunology

References

This article includes 67 references
  1. Hansen PJ, Dobbs KB, Denicol AC. Programming of the Preimplantation Embryo by the Embryokine Colony Stimulating Factor 2. Animal Reproduction Science 149, no. 1‐2 (2014): 59–66.
  2. Ealy AD, Speckhart SL, Wooldridge LK. Cytokines That Serve as Embryokines in Cattle. Animals 11, no. 8 (2021): 2313.
  3. Rose‐John S. Interleukin‐6 Family Cytokines. Cold Spring Harbor Perspectives in Biology 10, no. 2 (2018): a028415.
  4. Fedorka CE, Loux SL, Scoggin KE, Adams AA, Troedsson MHT, Ball BA. Alterations in T Cell‐Related Transcripts at the Feto‐Maternal Interface Throughout Equine Gestation. Placenta 89 (2020): 78–87.
  5. Fedorka CE, El‐Sheikh Ali H, Walker OF. The Imbalance of the Th17/Treg Axis Following Equine Ascending Placental Infection. Journal of Reproductive Immunology 144 (2021): 103268.
  6. Sang L, Ortiz W, Xiao Y, Estrada‐Cortes E, Jannaman EA, Hansen PJ. Actions of Putative Embryokines on Development of the Preimplantation Bovine Embryo to the Blastocyst Stage. Journal of Dairy Science 103, no. 12 (2020): 11930–11944.
  7. Tchirikov M, Schlabritz‐Loutsevitch N, Maher J. Mid‐Trimester Preterm Premature Rupture of Membranes (PPROM): Etiology, Diagnosis, Classification, International Recommendations of Treatment Options and Outcome. Journal of Perinatal Medicine 46, no. 5 (2018): 465–488.
  8. Leanos‐Miranda A, Nolasco‐Leanos AG, Carrillo‐Juarez RI, Molina‐Perez CJ, Isordia‐Salas I, Ramirez‐Valenzuela KL. Interleukin‐6 in Amniotic Fluid: A Reliable Marker for Adverse Outcomes in Women in Preterm Labor and Intact Membranes. Fetal Diagnosis and Therapy 48, no. 4 (2021): 313–320.
  9. Chaemsaithong P, Romero R, Korzeniewski SJ. A Rapid Interleukin‐6 Bedside Test for the Identification of Intra‐Amniotic Inflammation in Preterm Labor With Intact Membranes. The Journal of Maternal‐Fetal & Neonatal Medicine 29, no. 3 (2016): 349–359.
  10. Iwatani S, Kobayashi T, Ikuta T, Yoshida M, Yoshimoto S. Early Changes in Serum Interleukin‐6 Levels in Extremely Premature Newborns for Detecting Fetal Inflammation. Cytokine 176 (2024): 156528.
  11. Higgins RD, Saade G, Polin RA. Evaluation and Management of Women and Newborns With a Maternal Diagnosis of Chorioamnionitis: Summary of a Workshop. Obstetrics and Gynecology 127, no. 3 (2016): 426–436.
  12. Fedorka CE, Scoggin KE, El‐Sheikh Ali H. Interleukin‐6 Pathobiology in Equine Placental Infection. American Journal of Reproductive Immunology 85, no. 5 (2021): e13363.
  13. Loux SC, Conley AJ, Scoggin KE, El‐Sheikh Ali H, Dini P, Ball BA. New Insights in Equine Steroidogenesis: An In‐Depth Look at Steroid Signaling in the Placenta. Reproduction 160, no. 1 (2020): 65–82.
  14. El‐Sheikh Ali H, Boakari YL, Loux SC. Transcriptomic Analysis Reveals the Key Regulators and Molecular Mechanisms Underlying Myometrial Activation during Equine Placentitis†. Biology of Reproduction 102, no. 6 (2020): 1306–1325.
  15. Wagner B, Freer H. Development of a Bead‐Based Multiplex Assay for Simultaneous Quantification of Cytokines in Horses. Veterinary Immunology and Immunopathology 127, no. 3‐4 (2009): 242–248.
  16. Skogstrand K. Multiplex Assays of Inflammatory Markers, a Description of Methods and Discussion of Precautions—Our Experience Through the Last Ten Years. Methods 56, no. 2 (2012): 204–212.
  17. Kang S, Narazaki M, Metwally H, Kishimoto T. Historical Overview of the Interleukin‐6 Family Cytokine. Journal of Experimental Medicine 217, no. 5 (2020): e20190347.
  18. Lockwood CJ, Murk WK, Kayisli UA. Regulation of Interleukin‐6 Expression in Human Decidual Cells and Its Potential Role in Chorioamnionitis. American Journal of Pathology 177, no. 4 (2010): 1755–1764.
  19. Katsura D, Tsuji S, Hayashi K. Amniotic Fluid Interleukin‐6 and Neutrophil Gelatinase‐Associated Lipocalin for Predicting Fetal Inflammatory Response Syndrome Based on Histological Chorioamnionitis and Funisitis. Taiwanese Journal of Obstetrics and Gynecology 62, no. 4 (2023): 516–520.
  20. Wang Y, Gu Y, Alexander JS, Lewis DF. Preeclampsia Status Controls Interleukin‐6 and Soluble IL‐6 Receptor Release From Neutrophils and Endothelial Cells: Relevance to Increased Inflammatory Responses. Pathophysiology 28, no. 2 (2021): 202–211.
  21. Othman MA, Badawy ER, Sobh AMA, Shaltout AS, Mostafa SA. Effect of 17‐Hydroxyprogesterone Caproate on Interleukin‐6 and Tumor Necrosis Factor‐Alpha in Expectantly Managed Early‐Onset Preeclampsia. The Egyptian Journal of Immunology 30, no. 2 (2023): 109–118.
  22. Negi R, Haritha V, Aziz N, Siddiqui AH. Biochemical Markers in the Pathogenesis of Preeclampsia: Novel Link Between Placental Growth Factor and Interleukin‐6. Molecular and Cellular Biochemistry 477, no. 6 (2022): 1765–1774.
  23. Gupta S, Gaikwad HS, Nath B, Batra A. Can Vitamin C and Interleukin 6 Levels Predict Preterm Premature Rupture of Membranes: Evaluating Possibilities in North Indian Population. Obstetrics & Gynecology Science 63, no. 4 (2020): 432–439.
  24. El‐Ghazaly TE, Abdelazim IA, Elshabrawy A. Interleukin‐6 Bedside Test in Detecting Chorioamnionitis in Women With Preterm Premature Rupture of Fetal Membranes. Ginekologia Polska 93, no. 10 (2022): 835–841.
  25. Canzoneri BJ, Grotegut CA, Swamy GK. Maternal Serum Interleukin‐6 Levels Predict Impending Funisitis in Preterm Premature Rupture of Membranes After Completion of Antibiotics. The Journal of Maternal‐Fetal & Neonatal Medicine 25, no. 8 (2012): 1329–1332.
  26. Fedorka CE, Ball BA, Walker OF. Alterations of Circulating Biomarkers During Late Term Pregnancy Complications in the Horse Part I: Cytokines. Journal of Equine Veterinary Science 99 (2021): 103425.
  27. Fedorka CE, Ball BA, Scoggin KE, Loux SC, Troedsson MHT, Adams AA. The Feto‐Maternal Immune Response to Equine Placentitis. American Journal of Reproductive Immunology 82, no. 5 (2019): e13179.
  28. El‐Sheikh Ali H, Dini P, Scoggin K. Transcriptomic Analysis of Equine Placenta Reveals Key Regulators and Pathways Involved in Ascending Placentitis. Biology of Reproduction 104, no. 3 (2021): 638–656.
  29. Tribulo P, Siqueira LGB, Oliveira LJ, Scheffler T, Hansen PJ. Identification of Potential Embryokines in the Bovine Reproductive Tract. Journal of Dairy Science 101, no. 1 (2018): 690–704.
  30. Wooldridge LK, Ealy AD. Interleukin‐6 Increases Inner Cell Mass Numbers in Bovine Embryos. BMC Developmental Biology 19, no. 1 (2019): 2.
  31. Seekford ZK, Wooldridge LK, Dias NW. Interleukin‐6 Supplementation Improves Post‐Transfer Embryonic and Fetal Development of In Vitro‐Produced Bovine Embryos. Theriogenology 170 (2021): 15–22.
  32. Fedorka CE, Ball BA, Walker OF. Alteration of the Mare's Immune System by the Synthetic Progestin, Altrenogest. American Journal of Reproductive Immunology 82, no. 2 (2019): e13145.
  33. Garbers C, Scheller J. Interleukin‐6 and Interleukin‐11: Same Same but Different. Biological Chemistry 394, no. 9 (2013): 1145–1161.
  34. Garbers C, Hermanns HM, Schaper F. Plasticity and Cross‐Talk of Interleukin 6‐Type Cytokines. Cytokine & Growth Factor Reviews 23, no. 3 (2012): 85–97.
  35. Paiva P, Salamonsen LA, Manuelpillai U, Dimitriadis E. Interleukin 11 Inhibits Human Trophoblast Invasion Indicating a Likely Role in the Decidual Restraint of Trophoblast Invasion During Placentation. Biology of Reproduction 80, no. 2 (2009): 302–310.
  36. Allen WR, Hamilton DW, Moor RM. The Origin of Equine Endometrial Cups. II. Invasion of the Endometrium by Trophoblast. Anatomical Record 177, no. 4 (1973): 485–501.
  37. Pavlov OV, Selutin AV, Pavlova OM, Selkov SA. Two Patterns of Cytokine Production by Placental Macrophages. Placenta 91 (2020): 1–10.
  38. Makhseed M, Raghupathy R, Azizieh F, Omu A, Al‐Shamali E, Ashkanani L. Th1 and Th2 Cytokine Profiles in Recurrent Aborters With Successful Pregnancy and With Subsequent Abortions. Human Reproduction 16, no. 10 (2001): 2219–2226.
  39. Winship AL, Koga K, Menkhorst E. Interleukin‐11 Alters Placentation and Causes Preeclampsia Features in Mice. Proceedings of the National Academy of Sciences of the United States of America 112, no. 52 (2015): 15928–15933.
  40. Winship A, Menkhorst E, Van Sinderen M, Dimitriadis E. Interleukin 11 Blockade During Mid to Late Gestation Does Not Affect Maternal Blood Pressure, Pregnancy Viability or Subsequent Fertility in Mice. Reproductive Biomedicine Online 36, no. 3 (2018): 250–258.
  41. Wijelath ES, Carlsen B, Cole T, Chen J, Kothari S, Hammond WP. Oncostatin M Induces Basic Fibroblast Growth Factor Expression in Endothelial Cells and Promotes Endothelial Cell Proliferation, Migration and Spindle Morphology. Journal of Cell Science 110, no. pt 7 (1997): 871–879.
  42. David E, Tirode F, Baud'huin M. Oncostatin M Is a Growth Factor for Ewing Sarcoma. American Journal of Pathology 181, no. 5 (2012): 1782–1795.
  43. Ravelojaona M, Girouard J, Kana Tsapi ES. Oncostatin M and STAT3 Signaling Pathways Support Human Trophoblast Differentiation by Inhibiting Inflammatory Stress in Response to IFNgamma and GM‐CSF. Cells 13, no. 3 (2024): 229.
  44. Ko HS, Kang HK, Kim HS, Choi SK, Park IY, Shin JC. The Effects of Oncostatin M on Trophoblast Cells: Influence on Matrix Metalloproteinases‐2 and ‐9, and Invasion Activity. Placenta 33, no. 11 (2012): 908–913.
  45. Ko HS, Choi SK, Kang HK. Oncostatin M Stimulates Cell Migration and Proliferation by Down‐Regulating E‐Cadherin in HTR8/SVneo Cell Line Through STAT3 Activation. Reproductive Biology and Endocrinology [Electronic Resource]: RB&E 11 (2013): 93.
  46. Chang SH, Hwang CS, Yin JH, Chen SD, Yang DI. Oncostatin M‐Dependent Mcl‐1 Induction Mediated by JAK1/2‐STAT1/3 and CREB Contributes to Bioenergetic Improvements and Protective Effects Against Mitochondrial Dysfunction in Cortical Neurons. Biochimica Et Biophysica Acta 1853, no. 10 pt A (2015): 2306–2325.
  47. Ogata I, Shimoya K, Moriyama A. Oncostatin M Is Produced During Pregnancy by Decidual Cells and Stimulates the Release of HCG. Molecular Human Reproduction 6, no. 8 (2000): 750–757.
  48. Si ZP, Wang G, Han SS. CNTF and Nrf2 Are Coordinately Involved in Regulating Self‐Renewal and Differentiation of Neural Stem Cell During Embryonic Development. Iscience 19 (2019): 303–315.
  49. Akahori Y, Takamoto N, Masumoto A. Circulating Levels of Ciliary Neurotrophic Factor in Normal Pregnancy and Preeclampsia. Acta Medica Okayama 64, no. 2 (2010): 129–136.
  50. Tossetta G, Fantone S, Busilacchi EM. Modulation of Matrix Metalloproteases by Ciliary Neurotrophic Factor in Human Placental Development. Cell and Tissue Research 390, no. 1 (2022): 113–129.
  51. Pennica D, Swanson TA, Shaw KJ. Human Cardiotrophin‐1: Protein and Gene Structure, Biological and Binding Activities, and Chromosomal Localization. Cytokine 8, no. 3 (1996): 183–189.
  52. Briana DD, Germanou K, Boutsikou M. Potential Prognostic Biomarkers of Cardiovascular Disease in Fetal Macrosomia: The Impact of Gestational Diabetes. The Journal of Maternal‐Fetal & Neonatal Medicine 31, no. 7 (2018): 895–900.
  53. Kale I, Dizdar M. Investigation of Maternal Serum Cardiotrophin‐1 Concentrations in Pregnant Women With Preeclampsia: A Prospective Case‐Control Study. The Journal of Maternal‐Fetal & Neonatal Medicine 36, no. 2 (2023): 2229931.
  54. Boerboom D, Brown KA, Vaillancourt D. Expression of Key Prostaglandin Synthases in Equine Endometrium During Late Diestrus and Early Pregnancy. Biology of Reproduction 70, no. 2 (2004): 391–399.
  55. Oberg HH, Wesch D, Grussel S, Rose‐John S, Kabelitz D. Differential Expression of CD126 and CD130 Mediates Different STAT‐3 Phosphorylation in CD4+CD25‐ and CD25high Regulatory T Cells. International Immunology 18, no. 4 (2006): 555–563.
  56. Zhao S, Gu Y, Dong Q, Fan R, Wang Y. Altered Interleukin‐6 Receptor, IL‐6R and gp130, Production and Expression and Decreased SOCS‐3 Expression in Placentas from Women With Pre‐Eclampsia. Placenta 29, no. 12 (2008): 1024–1028.
  57. Dame JB, Juul SE. The Distribution of Receptors for the Pro‐Inflammatory Cytokines Interleukin (IL)‐6 and IL‐8 in the Developing Human Fetus. Early Human Development 58, no. 1 (2000): 25–39.
  58. Silver JS, Hunter CA. gp130 at the Nexus of Inflammation, Autoimmunity, and Cancer. Journal of Leukocyte Biology 88, no. 6 (2010): 1145–1156.
  59. Stahl N, Boulton TG, Farruggella T. Association and Activation of Jak‐Tyk Kinases by CNTF‐LIF‐OSM‐IL‐6 Beta Receptor Components. Science 263, no. 5143 (1994): 92–95.
  60. Lutticken C, Wegenka UM, Yuan J. Association of Transcription Factor APRF and Protein Kinase Jak1 With the Interleukin‐6 Signal Transducer gp130. Science 263, no. 5143 (1994): 89–92.
  61. Rose‐John S. IL‐6 Trans‐Signaling via the Soluble IL‐6 Receptor: Importance for the Pro‐Inflammatory Activities of IL‐6. International Journal of Biological Sciences 8, no. 9 (2012): 1237–1247.
  62. Lokau J, Agthe M, Garbers C. Generation of Soluble Interleukin‐11 and Interleukin‐6 Receptors: A Crucial Function for Proteases During Inflammation. Mediators of Inflammation 2016 (2016): 1785021.
  63. Diveu C, Venereau E, Froger J. Molecular and Functional Characterization of a Soluble Form of Oncostatin M/Interleukin‐31 Shared Receptor. Journal of Biological Chemistry 281, no. 48 (2006): 36673–36682.
  64. Allen WR. Maternal Recognition of Pregnancy and Immunological Implications of Trophoblast‐Endometrium Interactions in Equids. Ciba Foundation Symposium no. 64 (1978): 323–352.
  65. Antczak DF, de Mestre AM, Wilsher S, Allen WR. The Equine Endometrial Cup Reaction: A Fetomaternal Signal of Significance. Annual Review of Animal Biosciences 1 (2013): 419–442.
  66. Legacki EL, Ball BA, Corbin CJ. Equine Fetal Adrenal, Gonadal and Placental Steroidogenesis. Reproduction 154, no. 4 (2017): 445–454.
  67. Ball BA. Embryonic Loss in Mares. Incidence, Possible Causes, and Diagnostic Considerations. The Veterinary Clinics of North America Equine Practice 4, no. 2 (1988): 263–290.
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