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Role of progesterone in TLR4-MyD88-dependent signaling pathway in pre-eclampsia

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Summary

The role of progesterone in the Toll-like receptor 4 (TLR4)-MyD88-dependent signaling pathway in pre-eclampsia was studied. Peripheral blood mononuclear cells (PBMCs) from pre-eclampsia (PE) patients were subjected to primary culture, and stimulated with different concentrations of progesterone (0, 10−8, 10−6, and 10−4 mol/L). The mRNA expression of TLR4, MyD88 and nuclear factor-kappaB (NF-κB) was detected by using real-time PCR. The Ikappa-B protein expression was detected by using Western blotting. The expression of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in the supernatant was determined by using ELISA. With the concentrations of progesterone increasing, the mRNA expression levels of TLR4, MyD88 and NF-κB in 2−ΔΔCT value were significantly decreased, and the IkappaB protein expression levels were significantly increased. The TNF-α and IL-6 expression showed a downward trend when the progesterone concentration increased, and there were significant differences among all of the groups (P<0.05). It was suggested that progesterone can inhibit the TLR4-MyD88-dependent signaling pathway in PE significantly and benefit for the pregnancy.

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References

  1. Myatt L. Role of placenta in preeclampsia. Endocrine, 2002,19(1):103–111

    Article  PubMed  CAS  Google Scholar 

  2. Kim YM, Romero R, Oh SY, et al. Toll-like receptor 4: a potential link between “danger signals”, the innate immune system, and pre-eclampsia. Am J Obstet Gynecol, 2005,193(32):921–927

    PubMed  CAS  Google Scholar 

  3. Abrahams VM, Visintin I, Aldo PB, et al. A role for TLRs in the regulation of immune cell migration by first trimester trophoblast cells. Immunol, 2005, 175(12):8096–8104

    CAS  Google Scholar 

  4. Abramhen VM, Bole-aldo YM. KIM, et al. Divergent trophoblast responses to bacterial products mediated by TLRs. Immune, 2004,17(3):4286–4296

    Google Scholar 

  5. Medzhitov R, Janeway CA Jr. Decoding the patterns of self and nonself by the innate immune system. Science, 2002,296(5566):298–300

    Article  PubMed  CAS  Google Scholar 

  6. Akira S, Takeda K, Kaisho T. Toll-like receptors, critical proteins linking innate and acquired immunity. Nat Immunol, 2001,2(8):675–680

    Article  PubMed  CAS  Google Scholar 

  7. O’Neill LA. The Toll/interleukin-1 receptor domain: a molecular switch for inflammation and host defence. Biochem Soc Trans, 2000,28(5):557–563

    PubMed  Google Scholar 

  8. Faure E, Equils O, Sieling PA, et al. Bacterial lipopolysaccharide activates NF-kappaB through toll-like receptor 4 (TLR-4) in cultured human dermal endothelial cells. Differential expression of TLR-4 and TLR-2 in endothelial cells. Biol Chem, 2000,275(15):11 058–11 063

    CAS  Google Scholar 

  9. Chen G, Shi J, Jin W, et al. Progesterone administration modulates TLRs/NF-kappaB signaling pathway in rat brain after cortical contusion. Ann Clin Lab Sci, 2008,38(1):65–74

    PubMed  CAS  Google Scholar 

  10. Karin M, Cao Y, Greten FR, et al. NF-kappaB in cancer: from innocent bystander to major culprit. Nat Rev Cancer, 2002,2(4):301–310

    Article  PubMed  CAS  Google Scholar 

  11. Hayden MS, Ghosh S. Shared principles in NF-κB signaling. Cell, 2008,132(3):344–362

    Article  PubMed  CAS  Google Scholar 

  12. Medzhitov R, Janeway CJ. Innate immunity. N Engl J Med, 2000,343(5):338–344

    Article  PubMed  CAS  Google Scholar 

  13. Kawai T, Akira S. The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors. Nat Immunol, 2010,11(5):373–384

    Article  PubMed  CAS  Google Scholar 

  14. Faas MM, Schuiling GA, Baller JF, et al. A new animal model for human preeclampsia: ultra-low-dose endotoxin infusion in pregnant rats. Am J Obstet Gynecol, 1994, 171(1):158–164

    Article  PubMed  CAS  Google Scholar 

  15. Faas MM, Broekema M, Moes H, et al. Altered monocyte function in experimental preeclampsia in the rat. Am J Obstet Gynecol, 2004,191(4):1192–1198

    Article  PubMed  CAS  Google Scholar 

  16. Xia GQ, Xu DF, Wu M, et al. Expression of Toll-like receptor 4 in neonatal cord blood mononuclear cells in patients with preeclampsia. J Huazhong Univ Sci Technol [Med Sci], 2010,30(5):615–619

    Article  CAS  Google Scholar 

  17. Miller L, Hunt JS. Regulation of TNF-alpha production in activated mouse macrophages by progesterone. Immunol, 1998,160(10):5098–5104

    CAS  Google Scholar 

  18. Yuan Y, Shimizu I, Shen M, et al. Effects of estradiol and progesterone on the proinflammatory cytokine production by mononuclear cells from patients with chronic hepatitis C. World J Gastroenterol, 2008,4(14):2200–2207

    Article  Google Scholar 

  19. Wang Z, Zuo G, Shi XY, et al. Progesterone administration modulates cortical TLR4/NF-κB signaling pathway after subarachnoid hemorrhage in male rats. Mediators Inflamm, 2011,2011:848309

    Article  PubMed  Google Scholar 

  20. Jones LA, Anthony JP, Henriquez FL, et al. Toll-like receptor-4-mediated macrophage activation is differentially regulated by progesterone via the glucocorticoid and progesterone receptors. Immunology, 2008,125(1):59–69

    Article  PubMed  CAS  Google Scholar 

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Correspondence to Ge-qing Xia  (夏革清).

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Zhu, Y., Wu, M., Wu, Cy. et al. Role of progesterone in TLR4-MyD88-dependent signaling pathway in pre-eclampsia. J. Huazhong Univ. Sci. Technol. [Med. Sci.] 33, 730–734 (2013). https://doi.org/10.1007/s11596-013-1188-6

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  • DOI: https://doi.org/10.1007/s11596-013-1188-6

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