Stress ossidativo e invecchiamento : l'inattivazione dell'istone-deacetilasi, chiave di volta nella resistenza agli steroidi in pazienti con broncopneumopatia cronica ostruttiva (BPCO)

Inflammatory lung diseases are characterized by increased expression of multiple inflammatory genes that are regulated by pro-inflammatory transcription factors such as nuclear factor-κB and AP-1. Gene expression is regulated by acetylation of core histones through the action of activators with intrinsic histone acetyltransferase activity. Conversely gene repression is mediated via histone deacetylases and other corepressors. By contrast with patients with asthma, those with chronic obstructive pulmonary disease (COPD) are poorly responsive to the anti-inflammatory action of steroids and these drugs provide little clinical benefit. Steroids recruit histone deacetylase-2 (HDAC2) to the actively transcribing gene, which switches of inflammatory gene transcription. It is proposed that in patients with COPD, HDAC2 function is impaired by cigarette smoking and oxidative stress, leading to a pronounced reduction in responsiveness to corticosteroids. This proposal rises the possibility that novel therapeutic approaches might unlock this corticosteroids resistance, leading to more effective anti-inflammatory treatments for COPD and other severe inflammatory diseases.