title: Leukotriene E4 induces MUC5AC release from human airway epithelial NCI-H292 cells.
abstract: BACKGROUND
  Hypersecretion of mucin in the airway epithelium is an important feature of allergic airway diseases. Of the 3 cysteinyl leukotrienes (CysLTs; LTC4 LTD4 and LTE4), only LTE4 is sufficiently stable to be detectable in extracellular fluids. However, LTE4 has received little attention because it binds poorly to the CysLT1 and CysLT2 receptors; therefore, little is known about the effects of LTE4 on mucous secretion. Recently, studies have focused on the P2Y12 receptor as a potential receptor for LTE4, because this receptor is required for LTE4-mediated pulmonary inflammation. In our previous study, we confirmed the expression of P2Y12 receptor in human airway epithelial cells. To clarify the roles of LTE4 in airway epithelial cells, we investigated mucus secretion by LTE4 in vitro.
  
  
  METHODS
  Confluent NCI-H292 cells were stimulated with LTE4 (0.01-1 μM) for 24 h. The release and production of MUC5AC protein, a gel-forming mucin, were evaluated with an enzyme-linked immunosorbent assay.
  
  
  RESULTS
  Western blot analysis revealed that NCI-H292 cells expressed P2Y12 receptor protein. LTE4 significantly induced the release of MUC5AC mucin in a dose-dependent manner. Th2 cytokines such as IL-4 (10 ng/mL) and IL-13 (10 ng/mL) accelerated the LTE4-induced release of MUC5AC protein. MRS2935, a P2Y12 receptor antagonist, partially inhibited the LTE4-induced release of MUC5AC protein in the airway. In contrast, MK571, a CysLT1 receptor antagonist, did not affect the release of MUC5AC protein elicited by LTE4.
  
  
  CONCLUSIONS
  These results suggest that LTE4 may play some important roles in allergic mucus secretion partially via activation of P2Y12 receptor.
authors.affiliation: Department of Otolaryngology, Sapporo Medical University, School of Medicine, Hokkaido, Japan. Electronic address: shira@sapmed.ac.jp.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Shirasaki
authors.affiliation: Department of Otolaryngology, Sapporo Medical University, School of Medicine, Hokkaido, Japan.
authors.forename: Etsuko
authors.initials: E
authors.lastname: Kanaizumi
authors.affiliation: Department of Otolaryngology, Sapporo Medical University, School of Medicine, Hokkaido, Japan.
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Seki
authors.affiliation: Department of Otolaryngology, Sapporo Medical University, School of Medicine, Hokkaido, Japan.
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Himi
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D002460:Cell Line; D002478:Cells, Cultured; D004815:Epidermal Growth Factor / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D018793:Interleukin-13 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D017999:Leukotriene E4 / Q000494:pharmacology*; D055271:Mucin 5AC / Q000378:metabolism*; D058921:Purinergic P2Y Receptor Antagonists / Q000494:pharmacology; D058925:Receptors, Purinergic P2Y12 / Q000378:metabolism*; D014212:Tretinoin / Q000494:pharmacology; D014631:Valerates / Q000494:pharmacology
chemical_list: C528918:2,2-dimethylpropionic acid 3-(2-chloro-6-methylaminopurin-9-yl)-2-(2,2-dimethylpropionyloxymethyl)propyl ester; D018793:Interleukin-13; D055271:Mucin 5AC; C548576:P2RY12 protein, human; D058921:Purinergic P2Y Receptor Antagonists; D058925:Receptors, Purinergic P2Y12; D014631:Valerates; D015847:Interleukin-4; D014212:Tretinoin; D004815:Epidermal Growth Factor; D017999:Leukotriene E4; D000225:Adenine
keywords: Allergic mucous secretion; Epithelial cells; Leukotriene E(4); MUC5AC mucin; P2Y(12) antagonist