Cigarette Smoke and Estrogen Signaling in Human Airway Smooth Muscle

Venkatachalem Sathish, Michelle R. Freeman, Emma Long, Michael A. Thompson, Christina M. Pabelick, Y. S. Prakash

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

Aims: Cigarette smoke (CS) in active smokers and second-hand smoke exposure exacerbate respiratory disorders such as asthma and chronic bronchitis. While women are known to experience a more asthmatic response to CS than emphysema in men, there is limited information on the mechanisms of CS-induced airway dysfunction. We hypothesize that CS interferes with a normal (protective) bronchodilatory role of estrogens, thus worsening airway contractility. Methods: We tested effects of cigarette smoke extract (CSE) on 17β-estradiol (E 2 ) signaling in enzymatically-dissociated bronchial airway smooth muscle (ASM) obtained from lung samples of non-smoking female patients undergoing thoracic surgery. Results: In fura-2 loaded ASM cells, CSE increased intracellular calcium ([Ca 2+ ] i ) responses to 10μM histamine. Acute exposure to physiological concentrations of E 2 decreased [Ca 2+ ] i responses. However, in 24h exposed CSE cells, although expression of estrogen receptors was increased, the effect of E 2 on [Ca 2+ ] i was blunted. Acute E 2 exposure also decreased store-operated Ca 2+ entry and inhibited stromal interaction molecule 1 (STIM1) phosphorylation: effects blunted by CSE. Acute exposure to E 2 increased cAMP, but less so in 24h CSE-exposed cells. 24h CSE exposure increased S-nitrosylation of ERα. Furthermore, 24h CSE-exposed bronchial rings showed increased bronchoconstrictor agonist responses that were not reduced as effectively by E 2 compared to non-CSE controls. Conclusion: These data suggest that CS induces dysregulation of estrogen signaling in ASM, which could contribute to increased airway contractility in women exposed to CS.

Original languageEnglish (US)
Pages (from-to)1101-1115
Number of pages15
JournalCellular Physiology and Biochemistry
Volume36
Issue number3
DOIs
StatePublished - Jul 13 2015

Keywords

  • Bronchoconstriction
  • Bronchodilation
  • Calcium Regulation
  • Estrogen Receptor
  • Lung
  • STIM1
  • Secondhand Smoke
  • Sex Steroid
  • Store operated calcium entry

ASJC Scopus subject areas

  • Physiology

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