The Korean Journal of Physiology and Pharmacology

The Korean Society of Pharmacology (대한약리학회)
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Luteolin reduces fluid hypersecretion by inhibiting TMEM16A in interleukin-4 treated Calu-3 airway epithelial cells

  • Kim, Hyun Jong (Department of Physiology, Dongguk University College of Medicine) ;
  • Woo, JooHan (Department of Physiology, Dongguk University College of Medicine) ;
  • Nam, Yu-Ran (Channelopathy Research Center (CRC), Dongguk University College of Medicine) ;
  • Seo, Yohan (College of Pharmacy, Yonsei Institute of Pharmaceutical Sciences, Yonsei University) ;
  • Namkung, Wan (College of Pharmacy, Yonsei Institute of Pharmaceutical Sciences, Yonsei University) ;
  • Nam, Joo Hyun (Department of Physiology, Dongguk University College of Medicine) ;
  • Kim, Woo Kyung (Channelopathy Research Center (CRC), Dongguk University College of Medicine)
  • Received : 2020.03.03
  • Accepted : 2020.04.20
  • Published : 2020.07.01
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Abstract

Rhinorrhea in allergic rhinitis (AR) is characterized by the secretion of electrolytes in the nasal discharge. The secretion of Cl- and HCO3- is mainly regulated by cystic fibrosis transmembrane conductance regulator (CFTR) or via the calcium-activated Cl- channel anoctamin-1 (ANO1) in nasal gland serous cells. Interleukin-4 (IL-4), which is crucial in the development of allergic inflammation, increases the expression and activity of ANO1 by stimulating histamine receptors. In this study, we investigated ANO1 as a potential therapeutic target for rhinorrhea in AR using an ANO1 inhibitor derived from a natural herb. Ethanolic extracts (30%) of Spirodela polyrhiza (SPEtOH) and its five major flavonoids constituents were prepared. To elucidate whether the activity of human ANO1 (hANO1) was modulated by SPEtOH and its chemical constituents, a patch clamp experiment was performed in hANO1-HEK293T cells. Luteolin, one of the major chemical constituents in SPEtOH, significantly inhibited hANO1 activity in hANO1-HEK293T cells. Further, SPEtOH and luteolin specifically inhibited the calcium-activated chloride current, but not CFTR current in human airway epithelial Calu-3 cells. Calu-3 cells were cultured to confluency on transwell inserts in the presence of IL-4 to measure the electrolyte transport by Ussing chamber. Luteolin also significantly inhibited the ATP-induced increase in electrolyte transport, which was increased in IL-4 sensitized Calu-3 cells. Our findings indicate that SPEtOH and luteolin may be suitable candidates for the prevention and treatment of allergic rhinitis. SPEtOH- and luteolin-mediated ANO1 regulation provides a basis for the development of novel approaches for the treatment of allergic rhinitis-induced rhinorrhea.

Keywords

References

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