Estradiol Increases Mucus Synthesis in Bronchial Epithelial Cells

Tam, Anthony Raymond; Wadsworth, Samuel J.; Dorscheid, Delbert R.; Man, SF Paul; Sin, Don D.

doi:10.1371/journal.pone.0100633

Cited by 68 publications

(60 citation statements)

References 28 publications

(34 reference statements)

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“…Surprisingly, ovarian hormones increased Alt Ext-induced mucus production even though ovarian hormones did not increase IL-13+ ILC2. Previous reports have shown that estrogen, signaling through estrogen receptor-β, increased MUC5AC expression and mucus production in cultured airway epithelial cells (Tam et al, 2014), suggesting that sex hormones may regulate mucus production through multiple pathways. Our studies did not determine the mechanisms by which ovarian hormones regulated ILC2-induced airway inflammation nor take into account other cell types, including T cells, macrophages, and dendritic cells that sex hormones are known to regulate (Fuseini and Newcomb, 2017).…”

Section: Discussionmentioning

confidence: 96%

Testosterone Attenuates Group 2 Innate Lymphoid Cell-Mediated Airway Inflammation

et al. 2017

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Summary Sex hormones regulate many autoimmune and inflammatory diseases, including asthma. As adults, asthma prevalence is 2-fold greater in women compared to men. Group 2 innate lymphoid cells (ILC2) are increased in asthma, and we investigated how testosterone attenuated ILC2 function. In patients with moderate to severe asthma, we determined that women had increased circulating ILC2 numbers compared to men. In mice, ILC2 from adult females had increased IL-2-mediated ILC2 proliferation versus ILC2 from adult males and pre-pubescent females and males. Further, 5α-dihydrotestosterone, a hormone downstream of testosterone, decreased lung ILC2 numbers and IL-5 and IL-13 expression from ILC2. In vivo, testosterone attenuated Alternaria extract-induced IL-5+ and IL-13+ ILC2 numbers and lung eosinophils by intrinsically decreasing lung ILC2 numbers and cytokine expression as well as decreasing expression of IL-33 and TSLP, ILC2 stimulating cytokines. Collectively, these findings provide a foundational understanding in the sexual dimorphism in ILC2 function.

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Section: Discussionmentioning

confidence: 96%

Testosterone Attenuates Group 2 Innate Lymphoid Cell-Mediated Airway Inflammation

et al. 2017

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“…Administration of ethynyl oestradiol to guinea pigs significantly increased mucus cell hyperplasia compared to vehicle treated animals (79). Further, administration of estrogen or progesterone to cultured human airway or nasal epithelial cells the expression of the mucus proteins, Muc5AC and Muc5B, as well as mucus production when compared to vehicle treated cells (80, 81). Progesterone also decreased cilia beat frequency from cultured primary human airway epithelial cells, but cells that were co-administered 17b-E2 with progesterone had cilia beat frequency that was similar to vehicle treated cells (82).…”

Section: Role Of Sex Hormones In Airway Physiologymentioning

confidence: 99%

Mechanisms Driving Gender Differences in Asthma

Fuseini

Newcomb

2017

Curr Allergy Asthma Rep

334

226

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Purpose of Review Many phenotypes of asthma exist, ranging from mild asthma with onset during childhood to severe asthma with later onset, making asthma a broad disease with different pathologies. A gender disparity exists in asthma prevalence. As adults, women have an increased asthma prevalence compared to men. Further, women are more likely to have severe asthma and a later onset of asthma compared to men. Here, we review clinical and animal studies that have defined the role of sex hormones in airway inflammation, smooth muscle contraction, mucus production, and airway mechanics associated with asthma pathogenesis. Recent Findings Clinical evidence shows that increased asthma symptoms occur in females starting at puberty compared to boys. However, after puberty, the role for sex hormones in regulating asthma symptoms during menstruation, pregnancy, and menopause is not as clear. Animal studies have shown that estrogen increases and testosterone decreases Th2-mediated airway inflammation, and that females have increased IL-17A-mediated airway inflammation compared to males. Further, females had increased DC and Mφ function compared to males. However, the mechanisms driving the types of allergic inflammation are not fully elucidated. Summary Overall, ovarian hormones increased and testosterone decreased airway inflammation in asthma, but the mechanisms remain unclear. Delineating these pathways using animal models as well as women and men with various phenotypes of asthma will help determine if women with asthma should take (or avoid) hormonal contraceptives as well as predict changes asthma symptoms during life phases, including pregnancy and menopause, when sex hormones are dramatically changing.

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“…A recent report by Sheridan et al showed non-genomic estrogen inhibition of basal STIM1 phosphorylation followed by reduction in SOCE in airway epithelia (Sheridan et al, 2013). Estrogen also increases MUC5AC and is involved in post-translational modification (glycosylation) of mucins in human airways, this effect largely mediated by ERβ (Tam et al, 2014). Overall, these limited data suggest substantial effect of estrogens in the bronchial epithelium.…”

Section: Contribution Of Sex Steroids To Airway Structure and Funcmentioning

confidence: 99%

Sex steroid signaling: Implications for lung diseases

Sathish

Martin

Prakash

2015

Pharmacology & Therapeutics

137

134

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There is increasing recognition that the sex hormones (estrogen, progesterone, and testosterone) have biological and pathophysiological actions in peripheral, non-reproductive organs, including the lung. Clinically, sex differences in the incidence, morbidity and mortality of lung diseases such as asthma, chronic obstructive pulmonary disease (COPD), pulmonary fibrosis, lung cancer and pulmonary hypertension have been noted, although intrinsic sex differences vs. the roles of sex steroids are still not well-understood. Accordingly, it becomes important to ask the following questions: 1) Which sex steroids are involved? 2) How do they affect different components of the lung under normal circumstances? 3) How does sex steroid signaling change in or contribute to lung disease, and in this regard, are sex steroids detrimental or beneficial? As our understanding of sex steroid signaling in the lung improves, it is important to consider whether such information can be used to develop new therapeutic strategies to target lung diseases, perhaps in both sexes or in a sex-specific manner. In this review, we focus on the basics of sex steroid signaling, and the current state of knowledge regarding how they influence structure and function of specific lung components across the life span and in the context of some important lung diseases. We then summarize the potential for sex steroids as useful biomarkers and therapeutic targets in these lung diseases as a basis for future translational research in the area of gender and individualized medicine.

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Estradiol Increases Mucus Synthesis in Bronchial Epithelial Cells

Cited by 68 publications

References 28 publications

Testosterone Attenuates Group 2 Innate Lymphoid Cell-Mediated Airway Inflammation

Testosterone Attenuates Group 2 Innate Lymphoid Cell-Mediated Airway Inflammation

Mechanisms Driving Gender Differences in Asthma

Sex steroid signaling: Implications for lung diseases

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