Modulation of human β-defensin-2 expression by 17β-estradiol and progesterone in vaginal epithelial cells
Introduction
Human has been always exposed the various pathogens which are bacteria, fungus and virus, but it did not always make the clinical infections. These phenomena were thought to be concerned with antimicrobial peptides, very much important things in innate immunity of mammalian [1], [2].
α- and β-Defensins are antimicrobial peptides that are produced in epithelial cells of various organs and phagocytic cells. Human β-defensin (HBD)-1 and HBD-2 were known to be produced in various epithelial cells [3], [4], [5], [6], [7], [8], [9]. HBD-1 was constitutively produced in gastrointestinal tract, respiratory tract, mammary gland, skin, pancreas and kidney [3], [4], [5], [6]. HBD-2 was inducibly expressed in gastrointestinal tract, respiratory tract and pancreas by proinflammatory stimuli just like interleukin-1β, tumor necrotic factor-α and so on [3], [4], [7], [8].
Vaginal mucosa composed to squamous epithelial cells can be a target of bacterial vaginitis and the site of microbial pathogens’ colonization that causes genitourinary tract infection and therefore, innate host defense mediators like HBD-1 and -2 are supposed to be important in vaginal epithelium.
Estrogen and progesterone receptors exist in the vaginal epithelium. Estrogen prevents atrophy of vaginal epithelium and decreases susceptibility by preservation of low acidity and on the contrary, progesterone enhances vaginal atrophy or susceptibility to microbial pathogens [10], [11].
Microbial products induced a very quick and strong expression of HBD-2 in human vaginal epithelial cells and the concentration of HBD-2 in the vaginal lavage fluid of women with bacterial vaginosis was increased than healthy women [12], [13]. Urinary tract infection (UTI) was significantly increased by hormonal change in postmenopausal women [14], and sex hormones may have influence on innate host defense mechanism associated with antimicrobial peptides like defensins.
Therefore, we investigated the expression of HBD-1 and -2 in vaginal epithelial cells treated with lipopolysaccharide (LPS) and the effects on HBD-2 these expressions by 17β-estradiol and progesterone.
Section snippets
Cell culture and preparation
In order to harvest human vaginal epithelial cells, normal anterior vaginal wall obtained from vaginoplasty specimen was used. Experiments were performed in accordance with the recommendations of the Committee for the Protection of Persons and Animals at the Institute of Medical Science, Chung-Ang University, Seoul, Republic of Korea. The vaginal tissue fragments were washed by Ca2+-, Mg2+-free Hank’s balanced salt solution three times, and digested for 4 h in 0.05% trypsin–0.025% EDTA solution
The expression of HBD-1 mRNA by LPS, 17β-estradiol and combination
The expression of HBD-1 mRNA showed no difference between control, 17β-estradiol 2 nM, LPS 0.5 μg/ml, 17β-estradiol 2 nM + LPS 0.5 μg/ml after incubation for 12 h in vaginal epithelial cells (Fig. 1).
The expression of HBD-1 mRNA by LPS, progesterone and combination
The expression of HBD-1 mRNA showed no difference between control, progesterone 1 μM, LPS 0.5 μg/ml and progesterone 1 μM + LPS 0.5 μg/ml after incubation for 12 h in vaginal epithelial cells (Fig. 2).
The expression of HBD-2 mRNA by LPS, 17β-estradiol and combination
The expression of HBD-2 mRNA showed no difference between control and 17β-estradiol 2 nM, but showed the marked
Discussion
Bacterial vaginosis, characterized by a decreased concentration of lactobacilli and an overgrowth of a diverse community of bacteria [15], [16], is associated with genital tract infection. Vaginal or periurethral colonization is also the initial significant factor which causes UTI, and the vaginal and buccal mucosa of women susceptible to recurrent UTI were found to have greater adherence to microbial pathogens as compared with a control group [17], [18]. Vaginal mucosa is also liable to be
Conclusions
HBD-1 was produced constitutively in vaginal epithelial cells. HBD-2 was increased inducibly by LPS. Estrogen and progesterone did not influence the production of HBD-2 in normal state, but estrogen induced the production of HBD-2 and progesterone suppressed the production of HBD-2 under the circumstances with infection. Therefore, the lacks of estrogen during menopause or uses of a progesterone-based oral contraceptive with sexually active women may influence innate host defense mediators like
Conflict of interest
None.
Acknowledgements
This work was supported by a grant of the Korea Healthcare technology R&D Project, Ministry for Health, Welfare & Family Affairs, Republic of Korea (A085138). This funding source was only financial support and play no specific scientific role in this study.
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