The Cyclooxygenase-2–Prostaglandin E2 Pathway Maintains Senescence of Chronic Obstructive Pulmonary Disease Fibroblasts

Rationale: Chronic obstructive pulmonary disease (COPD) is associated with lung fibroblast senescence, a process characterized by the irreversible loss of replicative capacity associated with the secretion of inflammatory mediators. However, the mechanisms of this phenomenon remain poorly defined.Objectives: The aim of this study was to analyze the role of prostaglandin E2 (PGE2), a prostaglandin known to be increased in COPD lung fibroblasts, in inducing senescence and related inflammation in vitro in lung fibroblasts and in vivo in mice.Methods: Fibroblasts were isolated from patients with COPD and from smoker and nonsmoker control subjects. Senescence markers and inflammatory mediators were investigated in fibroblasts and in mice.Measurements and Main Results: Lung fibroblasts from patients with COPD exhibited higher expression of PGE2 receptors EP2 and EP4 as compared with nonsmoker and smoker control subjects. Compared with both nonsmoker and smoker control subjects, during long-term culture, COPD fi...