Potential Role of the Inflammasome-Derived Inflammatory Cytokines in Pulmonary Fibrosis

Abstract

Pulmonary fibrosis is a progressive, disabling disease with mortality rates that appear to be increasing in the western population, including the USA. There are over 140 known causes of pulmonary fibrosis as well as many unknown causes. Treatment options for this disease are limited due to poor understanding of the molecular mechanisms of the disease progression. However, recent progress in inflammasome research has greatly contributed to our understanding of its role in inflammation and fibrosis development. The inflammasome is a multiprotein complex that is an important component of both the innate and adaptive immune systems. Activation of proinflammatory cytokines following inflammasome assembly, such as IL-1β and IL-18, has been associated with development of PF. In addition, components of the inflammasome complex itself, such as the adaptor protein ASC have been associated with PF development. Recent evidence suggesting that the fibrotic process can be reversed via blockade of pathways associated with inflammasome activity may provide hope for future drug strategies. In this paper we will give an introduction to pulmonary fibrosis and its known causes. In addition, we will discuss the importance of the inflammasome in the development of pulmonary fibrosis as well as discuss potential future treatment options.

Evaluating the mechanistic evidence and key data gaps in assessing the potential carcinogenicity of carbon nanotubes and nanofibers in humans

“…Three mechanisms have been proposed for the release of proinflammatory mediators from lung macrophages following uptake of CNTs and other high-aspect ratio nanomaterials: (1) frustrated phagocytosis elicited by long, high-aspect ratio nanomaterials (Johnston et al 2010); (2) activation of the NLRP3 inflammasome leading to release of two key cytokines, IL-1β and IL-18 (Hamilton et al 2009; Palomaki et al 2011; Biswas et al 2011); and (3) release of alarmins, including IL-1α, IL-33, and high mobility group box protein (HMGB1) following cell necrosis (Chan et al 2012; Jessop & Holian 2014; Rabolli et al 2014). These proinflammatory mediators trigger continued recruitment of inflammatory cells and persistent inflammation (Grivennikov et al 2010).…”

Sintered Indium-Tin Oxide Particles Induce Pro-Inflammatory Responses In Vitro, in Part through Inflammasome Activation

“…However, how these particles initiate inflammatory responses and induce cellular damage leading to pulmonary disease remains unknown. Recent studies have implicated activation of the nod-like receptor protein 3 (NLRP3) inflammasome in the development of pulmonary fibrosis [ 15 – 17 ]. Inflammasome activation leads to the release of interleukin-1β (IL-1β), which unlike other cytokines requires not only transcriptional activation, but also activation of the cysteine protease caspase-1 to induce the processing and release of biologically active IL-1β.…”

Local administration of Trolox, a vitamin E analog, reduced tendon adhesion in a chicken model of flexor digitorum profundus tendon injury

“…The Animal Research Ethics Committee of the Chinese University of Hong Kong approved all animal experiments conducted in this study. A total of 54 3-month-old female Kamei chickens [Hong Kong Poultry (Kamei Chicken) Development Limited, Hong Kong] were used in this study; a well-established flexor digitorum profundus tendon injury animal model was used [11] , [12] . In brief, 1–1.5 mL of ketamine/xylazine (1:1) was intravenously injected to anesthetise the chicken.…”