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
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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