Skip to main content

Advertisement

SpringerLink
Log in

17β-Estradiol and Lipopolysaccharide Additively Promote Pelvic Inflammation and Growth of Endometriosis

  • Original Article
  • Published:
Reproductive Sciences Aims and scope Submit manuscript

Abstract

Endometriosis is a multifactorial disease mostly affecting women of reproductive age. An additive effect between inflammation and stress reaction on the growth of endometriosis has been demonstrated. Here we investigated the combined effect between 17β-estradiol (E2) and lipopolysaccharide (LPS) on pelvic inflammation and growth of endometriotic cells. Peritoneal fluid was collected from 46 women with endometriosis and 30 control women during laparoscopy. Peritoneal macrophages (Mφ) and stromal cells from eutopic/ectopic endometrial stromal cells (ESCs) were isolated from 10 women each with and without endometriosis in primary culture. Changes in cytokine secretion (interleukin 6 [IL-6] and tumor necrosis factor α [TNF-α]) by Mφ and proliferation of ESCs in response to single and combined treatment with E2 and LPS were measured by enzyme-linked immunosorbent assay and by bromodeoxyuridine incorporation assay, respectively. A significantly increased secretion of IL-6 and TNF-α in Mφ culture media was found in response to E2 (10−8 mol/L) compared to nontreated Mφ. This effect of E2 was abrogated after pretreatment of cells with ICI 182720 (10−6 mol/L; an estrogen receptor [ER] antagonist). Combined treatment with E2 and LPS (10 ng/mL) additively promoted IL-6 and TNF-α secretion by peritoneal Mφ and growth of eutopic/ectopic ESCs. The additive effects of E2 + LPS on cytokine secretion and growth of ESCs were effectively suppressed after combined blocking of ER and Toll-like receptor 4. An additive effect was observed between E2 and LPS on promoting proinflammatory response in pelvis and growth of endometriosis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Attar E, Bulun SE. Aromatase and other steroidogenic genes in endometriosis: translational aspects. Hum Reprod Update. 2006; 12(1):49–56.

    Article  CAS  Google Scholar 

  2. Burney RO, Giudice LC. Pathogenesis and pathophysiology of endometriosis. Fertil Steril. 2012;98(3):511–519.

    Article  CAS  Google Scholar 

  3. Khan KN, Kitajima M, Hiraki H, et al. Immunopathogenesis of pelvic endometriosis: role of hepatocyte growth factor, macrophages and ovarian steroids. Am J Reprod Immunol. 2008;60(5):383–404.

    Article  CAS  Google Scholar 

  4. Khan KN, Kitajima M, Hiraki K, et al. Escherichia coli contamination of menstrual blood and effect of bacterial endotoxin on endometriosis. Fertil Steril. 2010;94(7):2860–2863.

    Article  CAS  Google Scholar 

  5. Khan KN, Kitajima M, Inoue T, et al. Additive effects of inflammation and stress reaction on Toll-like receptor 4-mediated growth of endometriotic stromal cells. Hum Reprod. 2013;28(10):2794–2803.

    Article  CAS  Google Scholar 

  6. Straub RH. The complex role of estrogen in inflammation. Endocr Rev. 2007;28(5):521–574.

    Article  CAS  Google Scholar 

  7. Khan KN, Masuzaki H, Fujishita A, et al. Estrogen and progesterone receptor expression in macrophages and regulation of hepatocyte growth factor by ovarian steroids in women with endometriosis. Hum Reprod. 2005;20(7):2004–2013.

    Article  CAS  Google Scholar 

  8. Calippe B, Douin-Echinard V, Laffargue M, et al. Chronic estradiol administration in vivo promotes the pro-inflammatory response of macrophages to TLR4 activation: involvement of the phosphatidylinositol 3-kinase pathway. J Immunol. 2008;180(12):7980–7988.

    Article  CAS  Google Scholar 

  9. Khan KN, Masuzaki H, Fujishita A, et al. Association of interleukin-6 and estradiol with hepatocyte growth factor in peritoneal fluid of women with endometriosis. Acta Obstet Gynecol Scand. 2002;81(8):764–771.

    Article  Google Scholar 

  10. The American Society for Reproductive Medicine. Revised American Society for Reproductive Medicine classification of endometriosis: 1996. Fertil Steril. 1997;67(5):817–821.

    Article  Google Scholar 

  11. Kamiyama S, Teruya Y, Nohara M, Kanazawa K. Impact of detection of bacterial endotoxin in menstrual effluent on the pregnancy rate in in vitro fertilization and embryo transfer. Fertil Steril. 2004;82(4):788–792.

    Article  Google Scholar 

  12. Babson AL. Olson DR, Palmieri T, Rosss AF, Becker DM, Mulqueen PJ. The IMMULITE assay tube: a new approach to heterogenous ligand assay. Clin Chem. 1991;37(9):1521–1522.

    CAS  PubMed  Google Scholar 

  13. McLaren J, Prentice A, Charnock-Jones DS, et al. Vascular endothelial growth factor is produced by peritoneal fluid macrophages in endometriosis and is regulated by ovarian steroids. J Clin Invest. 1996;98(2):482–489.

    Article  CAS  Google Scholar 

  14. King AE, Collins F, Klonisch T, Sallenave JM, Critchley HOD, Saunders PTK. An additive interaction between the NFkB and estrogen receptor signaling pathways in human endometrial epithelial cells. Hum Reprod. 2010;25(2):510–518.

    Article  CAS  Google Scholar 

  15. Takagi S. Detection of 5-bromo-2-deoxyuridine (BrdU) incorporation with monoclonal anti-BrdU antibody after deoxyribonuclease treatment. Cytometry. 1993;14(6):640–649.

    Article  CAS  Google Scholar 

  16. Halme J, White C, Kauma S, Estes J, Haskill S. Peritoneal macrophages from patients with endometriosis release growth factor activity in vitro. J Clin Endocrinol Metab. 1988;66(5): 1044–1049.

    Article  CAS  Google Scholar 

  17. Halme J. Release of tumor necrosis factor-alpha by human peritoneal macrophages in vivo and in vitro. Am J Obstet Gynecol. 1989;161(6 pt 1):1718–1725.

    Article  CAS  Google Scholar 

  18. Cakmak H, Guzeloglu-Kayisli O, Kayisli UA, Arici A. Immuneendocrine interactions in endometriosis. Front Biosci. 2009;E1: 429–443.

    CAS  Google Scholar 

  19. Nirgianakis K, Bersinger NA, McKinnon B, Kostov P, Imboden S, Mueller MD. Regression of the inflammatory microenvironment of the peritoneal cavity in women with endometriosis by GnRHa treatment. Eur J Obstet Gynecol Reprod Biol. 2013; 170(2):550–554.

    Article  CAS  Google Scholar 

  20. Eischen A, Duclos B, Schmitt-Gognel M, et al. Human resident peritoneal macrophages: phenotype and histology. Br J Haematol. 1994;88(4):712–722.

    Article  CAS  Google Scholar 

  21. Khan KN, Kitajima M, Imamura T, et al. Toll-like receptor 4 (TLR4)-mediated growth of endometriosis by human heat shock protein 70 (Hsp70). Hum Reprod. 2008;23(10):2210–2219.

    Article  CAS  Google Scholar 

  22. Montagna P, Capellino S, Villaggio B, et al. Peritoneal fluid macrophages in endometriosis: correlation between the expression of estrogen receptors and inflammation. Fertil Steril. 2008; 90(1):156–164.

    Article  CAS  Google Scholar 

  23. Calippe B, Douin-Echinard V, Delpy L, et al. 17ß-Estradiol promotes TLR4-triggered pro-inflammatory mediator production through direct estrogen receptorα signaling in macrophages in vivo. J Immunol. 2010;185(2):1169–1176.

    Article  CAS  Google Scholar 

  24. Mor G, Sapi E, Abrahams VM, et al. Interaction of the estrogen receptors with the Fas ligand promoter in human monocytes. J Immunol. 2003;170(1):114–122.

    Article  CAS  Google Scholar 

  25. Kaponis A, Iwabe T, Taniguchi F, et al. The role of NF-kappaB in endometriosis. Front Biosci. 2012;S4:1568–1581.

    Article  Google Scholar 

  26. Kwon JH, Keates S, Simeonidis S, Grall F, Libermann TA, Keates AC. ESE-1, an enterocyte-specific Ets transcription factor, regulates MIP-3alpha gene expression in Caco-2 human colonic epithelial cells. J Biol Chem. 2003;278(2):875–884.

    Article  CAS  Google Scholar 

  27. Gruber CJ, Gruber DM, Gruber IM, Wieser F, Huber JC. Anatomy of the estrogen response element. Trends Endocrinol Metab. 2004;15(2):73–78.

    Article  CAS  Google Scholar 

  28. Falkenstein E, Tillmann HC, Christ M, Feuring M, Wehling M. Multiple actions of steroid hormones-a focus on rapid, nongenomic effects. Pharmacol Rev. 2000;52(4):513–556.

    CAS  PubMed  Google Scholar 

  29. Rettew JA, Huet YM, Marriott I. Estrogens augment cell surface TLR4 expression on murine macrophages and regulate sepsis susceptibility in vivo. Endocrinology. 2009;150(8):3877–3884.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Graduate School of Biomedical Sciences, Nagasaki University, 1-7-1 Sakamoto, 852-8501, Nagasaki, Japan

    Khaleque Newaz Khan MD, PhD, Michio Kitajima MD, PhD, Tsuneo Inoue MD, PhD & Hideaki Masuzaki MD, PhD

  2. Department of Gynecology, Saiseikai Nagasaki Hospital, Nagasaki, Japan

    Akira Fujishita MD, PhD

  3. Department of Tumor and Diagnostic Pathology, Atomic Bomb Disease Institute, Nagasaki, Japan

    Masahiro Nakashima MD, PhD

Authors
  1. Khaleque Newaz Khan MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Michio Kitajima MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Tsuneo Inoue MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Akira Fujishita MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Masahiro Nakashima MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Hideaki Masuzaki MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Khaleque Newaz Khan MD, PhD.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Khan, K.N., Kitajima, M., Inoue, T. et al. 17β-Estradiol and Lipopolysaccharide Additively Promote Pelvic Inflammation and Growth of Endometriosis. Reprod. Sci. 22, 585–594 (2015). https://doi.org/10.1177/1933719114556487

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1177/1933719114556487

Keywords

Search

Navigation