Mitochondrial Regulation of Inflammasome Activation in Chronic Obstructive Pulmonary Disease

Abstract

Chronic obstructive pulmonary disease (COPD) is characterized by enhanced chronic airway and lung inflammatory responses to noxious particles or gases. It is a major unmet medical need worldwide, and in Western society is strongly associated with exposure to cigarette smoke (CS). CS-induced inflammation is believed to be a key immune driver in the pathogenesis of COPD. Since the concept of inflammasomes was first introduced nearly a decade ago, these have been increasingly recognized as a central player in innate immune and inflammatory responses. In addition, studies have emerged demonstrating that mitochondrial innate immune signaling plays an important role in CS-induced inflammasome activation, pulmonary inflammation and tissue remodeling responses. Here, recent discoveries about inflammasome activation and mitochondrial biology and their role in COPD pathogenesis are reviewed. In addition, the current limitations of our understanding of this theme and future research directions are discussed.

Going Fishing

“…One of the best-characterized proteins within this family of inflammatory mediators is high mobility group box-1 (HMGB1) [15], but also extracellular histones and antimicrobial peptides (AMPs) have lately attracted significant attention [16]. Thus, it seems plausible that DAMPs provide the danger signals that the innate immune system needs to distinguish whether a PRR is activated by a commensal or pathogenic microorganism.…”

Is mitochondrial dysfunction a driving mechanism linking COPD to nonsmall cell lung carcinoma?

“…This is partially dependent on cigarette smoke activation of a critical adaptor molecule of the NLRP3 pathway, MAVS [117]. Inhibition of MAVS and NLRP3 inflammasome pathway could therefore reduce the chronic inflammation associated with COPD.…”

Full Complement

“…However, long-standing and dysregulated inflammation in the airways is a key feature of several states of disease, e.g., in COPD and cystic fibrosis [11][12][13]. Furthermore, without a preceding chronic airway inflammation, the host response may cause tissue damage [10,14].…”