Regulatory Effects of Estradiol on Peripheral Blood Mononuclear Cells Activation in Patients with Asthma

  • Abbas Ahmadi-Vasmehjani Department of Immunology and Microbiology, School of Medicine, Jahrom University of Medical Sciences, Jahrom, Iran
  • Rasoul Baharlou Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
  • Mohammad Reza Atashzar Department of Immunology and Microbiology, School of Medicine, Jahrom University of Medical Sciences, Jahrom, Iran
  • Rahim Raofi Department of Infectious Diseases, School of Medicine, Jahrom University of Medical Sciences, Jahrom, Iran
  • Mohammad Jafari Department of Immunology and Microbiology, School of Medicine, Jahrom University of Medical Sciences, Jahrom, Iran
  • Faezeh-Sadat Razavi Department of Student Research Committee, School of Medicine, Jahrom University of Medical Sciences, Jahrom, Iran
Keywords: Asthma, Estradiol, IL-17, IL-21, IL-23, TGF-β


Asthma prevalence and severity are greater in women than in men, and mounting evidence suggests this is in part related to female steroid sex hormones. Conflicting data are reported regarding pro- and anti-inflammatory properties of estradiol. This study was designed to clarify whether estradiol may contribute to enhanced T helper (Th) 17-associated cytokines production by peripheral blood mononuclear cells (PBMC) in asthmatic patients and healthy individuals. PBMCs from patients with asthma and healthy donors were cultured with 17-β estradiol (E2) and phytohemagglutinin (PHA). The quantitative real-time polymerase chain reaction (qRT-PCR) was used to measure IL-6, IL-17, IL-23 and TGF-β. We observed a significant increased IL-17, IL-23 and TGF-β expression in PBMCs of patients compared to the healthy individuals. In addition, our findings indicated that IL-6 and IL-17 expressions in PBMCs were induced, following E2 treatment. Our results identified an impact of E2 in stimulation of Th17 phenotype, and upon hormonal oscillations and hormone replacement therapy (HRT), asthma inflammation may be mediated by Th17-associated cytokines.


1. Kim H, Mazza J. Asthma. Allergy Asthma Clin Immunol 2011;7(Suppl 1):S2-S.2. Findlay J, Liew S, Simpson E, Korach K. Estrogen signaling in the regulation of female reproductive functions. Fertility Control: Springer; 2010;29-35.3. Dimitropoulou C, Drakopanagiotakis F, Chatterjee A, Snead C, Catravas JD. Estrogen replacement therapy prevents airway dysfunction in a murine model of allergen-induced asthma. Lung 2009;187(2):116-27.4. Walker SE. Estrogen and autoimmune disease. Clin Rev Allergy Immunol 2011;40(1):60-5.5. Bonds RS, Midoro-Horiuti T. Estrogen effects in allergy and asthma. Curr Opin Allergy Clin Immunol 2013;13(1):92.6. Ticconi C, Pietropolli A, Piccione E. Estrogen replacement therapy and asthma. Pulm Pharmacol Ther 2013;26(6):617-23.7. Leynaert B, Sunyer J, Garcia-Esteban R, Svanes C, Jarvis D, Cerveri I, et al. Gender differences in prevalence, diagnosis and incidence of allergic and non-allergic asthma: a population-based cohort. Thorax 2012;67(7):625-31.8. Tam A, Morrish D, Wadsworth S, Dorscheid D, Man SP, Sin DD. The role of female hormones on lung function in chronic lung diseases. BMC Womens Health 2011;11(1):24.9. Ghosh M, Rodriguez-Garcia M, Wira CR. The immune system in menopause: pros and cons of hormone therapy. J Steroid Biochem Mol Biol 2014;142:171-5.10. Carlsten H, D'Elia HF, Erlandsson M, Islander U. Menopause and hormone replacement therapy: effects on the immune system, arthritis and bone. Arthritis Res Ther 2004;6(3):1.11. Barr RG, Wentowski CC, Grodstein F, Somers SC, Stampfer MJ, Schwartz J, et al. Prospective study of postmenopausal hormone use and newly diagnosed asthma and chronic obstructive pulmonary disease. Arch Intern Med 2004;164(4):379-86.12. Executive G, Committee S. Global Initiative for Asthma (GINA). Global strategy for asthma management and prevention. 2014.13. Pfaffl MW. A new mathematical model for relative quantification in real-time RT–PCR. Nucleic Acids Res 2001;29(9):e45-e.14. Baharlou R, Ahmadi-Vasmehjani A, Davami MH, Faraji F, Atashzar MR, Karimipour F, et al. Elevated levels of T-helper 17-associated cytokines in diabetes type I patients: indicators for following the course of disease. Immunol Invest 2016;45(7):641-51.15. Wang Y-H, Wills-Karp M. The potential role of interleukin-17 in severe asthma. Curr Allergy Asthma Rep 2011;11(5):388-94.16. Nakajima H, Hirose K. Role of IL-23 and Th17 cells in airway inflammation in asthma. Immune Netw 2010;10(1):1-4.17. Makinde T, Murphy RF, Agrawal DK. The regulatory role of TGF-b in airway remodeling in asthma. Immunol Cell Biol 2007; 85(5):348-56.18. Rincon M, Irvin CG. Role of IL-6 in asthma and other inflammatory pulmonary diseases. Int J Biol Sci 2012;8(9):1281-90.19. Lim RH, Kobzik L. Sexual tension in the airways: the puzzling duality of estrogen in asthma. Am J Respir Cell Mol Biol 2008;38(5):499-500.20. Newcomb DC, Cephus JY, Boswell MG, Fahrenholz JM, Langley EW, Feldman AS, et al. Estrogen and progesterone decrease let-7f microRNA expression and increase IL-23/IL-23 receptor signaling and IL-17A production in patients with severe asthma.J Allergy Clin Immunol 2015;136(4):1025-34.21. Baker DCN, Cephus J-Y, Langley EW, Feldman AS, Frey N, Cooper K, et al. 17-β Estradiol Positively Correlates With IL-17A+ CCR6+ Memory CD4+ T Cells In Patients With Severe Asthma. Journal of Allergy and Clinical Immunology. 2014;133(2):AB91.22. Lélu K, Laffont S, Delpy L, Paulet P-E, Périnat T, Tschanz SA, et al. Estrogen receptor α signaling in T lymphocytes is required for estradiol-mediated inhibition of Th1 and Th17 cell differentiation and protection against experimental autoimmune encephalomyelitis. J Immunol 2011;187(5):2386-93.23. Baldacara RP, Silva I. Association between asthma and female sex hormones. SSao Paulo Med J 2017; 135(1):4-14.24. Calippe B, Douin-Echinard V, Laffargue M, Laurell H, Rana-Poussine V, Pipy B, et al. Chronic estradiol administration in vivo promotes the proinflammatory response of macrophages to TLR4 activation: involvement of the phosphatidylinositol 3-kinase pathway. J Immunol 2008;180(12):7980-8.25. Bengtsson ÅK, Ryan EJ, Giordano D, Magaletti DM, Clark EA. 17β-estradiol (E2) modulates cytokine and chemokine expression in human monocyte-derived dendritic cells. Blood 2004;104(5):1404-10.26. Siracusa MC, Overstreet MG, Housseau F, Scott AL, Klein SL. 17β-estradiol alters the activity of conventional and IFN-producing killer dendritic cells. J Immunol 2008;180(3):1423-31.27. Rachon D, Mysliwska J, Suchecka-Rachon K, Wieckiewicz J, Mysliwski A. Effects of oestrogen deprivation on interleukin-6 production by peripheral blood mononuclear cells of postmenopausal women. J Endocrinol 2002;172(2):387-95.28. Dong X, Xu M, Ren Z, Gu J, Lu M, Lu Q, et al. Regulation of CBL and ESR1 expression by microRNA-22‑3p, 513a-5p and 625-5p may impact the pathogenesis of dust mite-induced pediatric asthma. Int J Mol Med 2016; 38(2):446-56.29. Rogers A, Eastell R. The effect of 17β-estradiol on production of cytokines in cultures of peripheral blood. Bone 2001;29(1):30-4.30. Alcorn JF, Crowe CR, Kolls JK. TH17 cells in asthma and COPD. Annu Rev Physiol 2010;72:495-516.31. Park SJ, Lee YC. Interleukin-17 regulation: an attractive therapeutic approach for asthma. Respir Res 2010;11(1):78.32. Jaberipour M, Baharlou R, Hosseini A, Talei A, Razmkhah M, Ghaderi A. Increased il-17 and il-6 transcripts in peripheral blood mononuclear cells: Implication for a robust proinflammatory response in early stages of breast cancer. Middle East Journal of Cancer 2011; 2(1):19-26.33. Suzuki T, Yu H-P, Hsieh Y-C, Choudhry MA, Bland KI, Chaudry IH. Mitogen activated protein kinase (MAPK) mediates non-genomic pathway of estrogen on T cell cytokine production following trauma-hemorrhage. Cytokine 2008;42(1):32-8.34. Piccinni M-P, Giudizi M-G, Biagiotti R, Beloni L, Giannarini L, Sampognaro S, et al. Progesterone favors the development of human T helper cells producing Th2-type cytokines and promotes both IL-4 production and membrane CD30 expression in established Th1 cell clones.J Immunol 1995;155(1):128-33.35. Baharlou R, Ahmadi-Vasmehjani A, Faraji F, Atashzar MR, Khoubyari M, Ahi S, et al. Human adipose tissue-derived mesenchymal stem cells in rheumatoid arthritis: Regulatory effects on peripheral blood mononuclear cells activation. Int Immunopharmacol 2017;47:59-69.

How to Cite
Ahmadi-Vasmehjani A, Baharlou R, Atashzar MR, Raofi R, Jafari M, Razavi F-S. Regulatory Effects of Estradiol on Peripheral Blood Mononuclear Cells Activation in Patients with Asthma. ijaai. 17(1):9-7.
Original Article(s)