Background: Lung fibroblasts from Severe Early-Onset (SEO-)COPD patients show increased cellular senescence with higher levels of senescence-associated secretory phenotype (SASP) protein secretion. Yet, the impact of senescent fibroblasts, and their SASP, on other fibroblasts in COPD lungs remains unclear.

Aim: To identify the effect of the SASP secreted by senescent SEO-COPD lung fibroblasts on naïve lung fibroblasts.

Methods: Cellular senescence was induced in lung fibroblasts derived from seven SEO-COPD patients (age <53 years, FEV1 <40% predicted) and conditioned medium (CM), containing the SASP, was collected (senescent CM). CM from untreated fibroblasts was used as control (control CM). Naïve fibroblasts were treated with senescent and control CM. The effects on paracrine senescence (Senescence-Associated Beta-galactosidase (SA-?-gal), p16 & p21), inflammation (Interleukin (IL-)6 & IL-8), and decorin (DCN) secretion were assessed.

Results: Treatment with senescent CM induced an increase in SA-?-gal positive cells and decreased p16 & p21 expression (p<0.05). Senescent CM induced increases in IL-8 expression (3 fold change), and IL-6 & IL-8 secretion (1.6 & 6 fold change respectively) in recipient cells compared to control CM (p<0.05). In addition, senescent CM resulted in a 2.3 fold reduction in DCN secretion (p=0.02).

Conclusion: These results imply that the SASP from senescent SEO-COPD fibroblasts has a strong paracrine effect, resulting in a pro-inflammatory response and decreased DCN secretion in lung fibroblasts. These data show a potential contributing role of the SASP from senescent fibroblasts to inflammation and extracellular matrix remodeling in COPD lungs.