Estrogen receptors differentially regulate intracellular calcium handling in human nonasthmatic and asthmatic airway smooth muscle cells
Autor: | Venkatachalem Sathish, Jennifer Connell, Sangeeta Bhallamudi, Christina M. Pabelick, Y. S. Prakash |
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Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
Pulmonary and Respiratory Medicine medicine.medical_specialty Physiology medicine.drug_class Bronchoconstriction Myocytes Smooth Muscle Respiratory System chemistry.chemical_element Estrogen receptor Inflammation Calcium Calcium in biology Cell Line 03 medical and health sciences 0302 clinical medicine Physiology (medical) Internal medicine Estrogen Receptor beta Humans Medicine Interleukin-13 Estradiol Tumor Necrosis Factor-alpha business.industry Estrogen Receptor alpha Estrogens Muscle Smooth Cell Biology respiratory system Asthma respiratory tract diseases Sarcoplasmic Reticulum 030104 developmental biology Endocrinology chemistry Estrogen Sex steroid 030220 oncology & carcinogenesis medicine.symptom business Airway Muscle Contraction Signal Transduction Research Article |
Zdroj: | Am J Physiol Lung Cell Mol Physiol |
ISSN: | 1522-1504 1040-0605 |
Popis: | Asthma is defined as chronic inflammation of the airways and is characterized by airway remodeling, hyperresponsiveness, and acute bronchoconstriction of airway smooth muscle (ASM) cells. Clinical findings suggest a higher incidence and severity of asthma in adult women, indicating a concrete role of sex steroids in modulating the airway tone. Estrogen, a major female sex steroid mediates its role through estrogen receptors (ER) ERα and ERβ, which are shown to be expressed in human ASM, and their expression is upregulated in lung inflammation and asthma. Previous studies suggested rapid, nongenomic signaling of estrogen via ERs reduces intracellular calcium ([Ca2+]i), thereby promoting relaxation of ASM. However, long-term ER activation on [Ca2+]iregulation in human ASM during inflammation or in asthma is still not known. In Fura-2-loaded nonasthmatic and asthmatic human ASM cells, we found that prolonged (24 h) exposure to ERα agonist (PPT) increased [Ca2+]iresponse to histamine, whereas ERβ activation (WAY) led to decreased [Ca2+] compared with vehicle. This was further confirmed by ER overexpression and knockdown studies using various bronchoconstrictor agents. Interestingly, ERβ activation was more effective than 17β-estradiol in reducing [Ca2+]iresponses in the presence of TNF-α or IL-13, while no observable changes were noticed with PPT in the presence of either cytokine. The [Ca2+]i-reducing effects of ERβ were mediated partially via L-type calcium channel inhibition and increased Ca2+sequestration by sarcoplasmic reticulum.Overall, these data highlight the differential signaling of ERα and ERβ in ASM during inflammation. Specific ERβ activation reduces [Ca2+]iin the inflamed ASM cells and is likely to play a crucial role in regulating ASM contractility, thereby relaxing airways. |
Databáze: | OpenAIRE |
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