Differential Expression of Estrogen Receptor Variants in Response to Inflammation Signals in Human Airway Smooth Muscle

Bharathi Aravamudan, Katelyn J. Goorhouse, Ghanashyam Unnikrishnan, Michael A. Thompson, Christina M Pabelick, John R Hawse, Y.s. Prakash, Venkatachalem Sathish

Research output: Contribution to journalArticle

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Abstract

The prevalence of asthma is higher in pre-pubescent and aging males, and in post-pubertal females, strongly indicating that sex steroids (especially estrogen) may be an important modulator in lung disease. We recently demonstrated that airway smooth muscle (ASM) expresses both alpha and beta forms of the estrogen receptor (ERα and ERβ) in males and females, and that these receptors regulate intracellular [Ca2+] and ASM contractility. Although both ERα and ERβ have multiple splice variants, it is unclear if and how the expression of these variants is modulated under conditions such as chronic inflammation/asthma. In order to test the hypothesis that the differential expression of ERα and ERβ variants contributes to the pathogenesis of asthma, we profiled the expression of various ERα and ERβ genes in asthmatic and inflamed (TNFα- or IL-13-treated) ASM. Gene expression was assessed at both the mRNA and protein levels in asthmatic ASM cells or non-asthmatic cells treated with TNFα (20 ng/ml) or IL-13 (50 ng/ml). We observed marked variation in the expression of ER isoforms in response to inflammatory stimuli, and in non-asthmatic versus asthmatic ASM. Changes in protein levels of ERα and ERβ corresponded with the observed differential mRNA patterns. Pharmacological studies implicate cytosolic (p42/44 MAPK and PI3 K) and nuclear (NFκB, STAT6, and AP-1) signaling pathways as putative mechanisms that mediate and/or regulate effects of inflammation on ER expression. We conclude that variations in ASM ER expression profiles occur with inflammation and that ER variants could contribute to estrogen signaling in airway diseases such as asthma. J. Cell. Physiol. 232: 1754–1760, 2017.

Original languageEnglish (US)
Pages (from-to)1754-1760
Number of pages7
JournalJournal of Cellular Physiology
Volume232
Issue number7
DOIs
StatePublished - Jul 1 2017

Fingerprint

Estrogen Receptors
Smooth Muscle
Muscle
Inflammation
Asthma
Interleukin-13
Estrogens
Estrogen Receptor beta
Messenger RNA
Mitogen-Activated Protein Kinase 1
Transcription Factor AP-1
Lung Diseases
Smooth Muscle Myocytes
Pulmonary diseases
Protein Isoforms
Proteins
Steroids
Pharmacology
Gene expression
Modulators

ASJC Scopus subject areas

  • Medicine(all)
  • Physiology
  • Clinical Biochemistry
  • Cell Biology

Cite this

Differential Expression of Estrogen Receptor Variants in Response to Inflammation Signals in Human Airway Smooth Muscle. / Aravamudan, Bharathi; Goorhouse, Katelyn J.; Unnikrishnan, Ghanashyam; Thompson, Michael A.; Pabelick, Christina M; Hawse, John R; Prakash, Y.s.; Sathish, Venkatachalem.

In: Journal of Cellular Physiology, Vol. 232, No. 7, 01.07.2017, p. 1754-1760.

Research output: Contribution to journalArticle

Aravamudan, Bharathi ; Goorhouse, Katelyn J. ; Unnikrishnan, Ghanashyam ; Thompson, Michael A. ; Pabelick, Christina M ; Hawse, John R ; Prakash, Y.s. ; Sathish, Venkatachalem. / Differential Expression of Estrogen Receptor Variants in Response to Inflammation Signals in Human Airway Smooth Muscle. In: Journal of Cellular Physiology. 2017 ; Vol. 232, No. 7. pp. 1754-1760.
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