Luteolin reduces fluid hypersecretion by inhibiting TMEM16A in interleukin-4 treated Calu-3 airway epithelial cells

Rhftnorrhea ftn allergftc rhftnfttis (AR) fts characterftzed by the secretion of electrolytes ftn the nasal dftscharge. The secretion of Cl^? and HCO₃^? fts maftnly regulated by cystic fibrosfts transmembrane conductance regulator (CFTR) or vfta the calcftumactivated Cl^? channel anoctamftn-1 (ANO1) ftn nasal gland serous cells. Interleukftn-4 (IL-4), whftch fts crucftal ftn the development of allergftc ftnflammation, ftncreases the expressfton and activftty of ANO1 by stimulating hftstamftne receptors. In thfts study, we ftnvestigated ANO1 as a potential therapeutic target for rhftnorrhea ftn AR usftng an ANO1 ftnhftbfttor derftved from a natural herb. Ethanolftc extracts (30%) of Spirodela polyrhiza (SP_EtOH) and ftts five major flavonoftds constituents were prepared. To elucftdate whether the activftty of human ANO1 (hANO1) was modulated by SP_EtOH and ftts chemftcal constituents, a patch clamp experftment was performed ftn hANO1-HEK293T cells. Luteolftn, one of the major chemftcal constituents ftn SP_EtOH, sftgnftficantly ftnhftbftted hANO1 activftty ftn hANO1-HEK293T cells. Further, SP_EtOH and luteolftn specftfically ftnhftbftted the calcftum-activated chlorftde current, but not CFTR current ftn human aftrway epftthelftal Calu-3 cells. Calu-3 cells were cultured to confluency on transwell ftnserts ftn the presence of IL-4 to measure the electrolyte transport by Ussftng chamber. Luteolftn also sftgnftficantly ftnhftbftted the ATP-ftnduced ftncrease ftn electrolyte transport, whftch was ftncreased ftn IL-4 sensfttized Calu-3 cells. Our findftngs ftndftcate that SP_EtOH- and luteolftn may be sufttable candftdates for the prevention and treatment of allergftc rhftnfttis. SPEtOH- and luteolftn-medftated ANO1 regulation provftdes a basfts for the development of novel approaches for the treatment of allergftc rhftnfttis-ftnduced rhftnorrhea.