TLR3 over-expression triggered IL-8 release in human bronchial epithelial cells from smokers and smokers with COPD patients as well as in cells exposed to CSE, that was insensitive to corticosteroids but not to roflumilast N-oxide suggesting a prominent role of cigarette smoke on corticosteroid insensitivity. The gene discussed is TLR3; the disease is chronic obstructive pulmonary disease.