چکیده (انگلیسی):

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 (0.01e1 mM) 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.