In the present study, we evaluated the following points, using NCI-H292 cells and differentiated primary human bronchial epithelial cells (HBECs) from normal subjects and COPD patients: (a) whether pannexin channels are involved in ATP release, (b) whether the inhibition of P2Rs, especially P2X7R and P2Y2R, affects MUC5AC production and the EGFR-ERK signaling pathway after stimulation with a synthetic dsRNA analogue, polyinosinic-polycytidylic acid [poly(I:C)], as a TLR3 ligand to mimic viral infection, and rhinovirus infection. This evidence concerns the gene TLR3 and viral infectious disease.