The Role of PPARy in Ageing Associated Pulmonary Diseases

Pulmonary tissue inflammation is often associated with ageing and may be triggered by various factors including infectious or chemical agents, but may also be initiated by endogenous factors as in the case of autoimmune conditions [74]. Despite the diversity of lung inflammation triggering factors the subsequently activated proinflammatory pathways are often shared. PPARy can efficiently act on these pathways as it inhibits transcription factors regulating the expression of pro-inflammatory genes such as NF-kB, STAT-1 and AP1 [75, 76]. Activated PPARy is capable of sequestering co-activator complexes on the promoter regions of pro-inflammatory genes that renders them inaccessible to these transcription factors. Also, PPARy activation leads to the production of suppressive mediators, such as TGFp and IL-10 that might be even more significant in the local micro-environment niche [77, 78]. As a consequence PPARy up-regulation potentiates inhibitory loops that provide the molecular basis for resolution following an initially inflammatory response.