17β-estradiol (E2) increases ciliary beat frequency via membrane estrogen receptor β

Estrogen receptors (ER) are expressed in various tissues, including the lungs and other respiratory tissues, independent of sex. However, the role of estrogen in the respiratory tract is not fully understood. Airway ciliated cells are important for mucociliary clearance (MCC), which protects the human airways from foreign substances, and ciliary beat frequency (CBF) is an important indicator of MCC efficiency. Although the function of estrogen in airway smooth muscle cells and goblet cells has been studied, its effects on airway ciliated cells remain unclear. Here, we investigated the effect of 17β-estradiol (E2) on CBF. E2 increased CBF and intracellular cAMP concentration ([cAMP]_i) in murine airway ciliated cells, whereas it had no effect on intracellular Ca^2 + concentration and intracellular pH. The selective ERβ inhibitor PHTPP suppressed the E2-induced increase in CBF and [cAMP]_i. β-Estradiol 6-(O-carboxymethyl)oxime: bovine serum albumin conjugate, which activates membrane ER, also increased CBF and [cAMP]_i in murine airway ciliated cells, and PHTPP suppressed these effects. The results of this study indicate that E2 increases CBF by increasing [cAMP]_i via membrane ERβ in murine airway ciliated cells. These results provide new insight into the function of estrogen in airway ciliated cells.