Mechanisms and Functions of Inflammasomes

Abstract

Recent studies have offered a glimpse into the sophisticated mechanisms by which inflammasomes respond to danger and promote secretion of interleukin (IL)-1β and IL-18. Activation of caspases 1 and 11 in canonical and noncanonical inflammasomes, respectively, also protects against infection by triggering pyroptosis, a proinflammatory and lytic mode of cell death. The therapeutic potential of inhibiting these proinflammatory caspases in infectious and autoimmune diseases is raised by the successful deployment of anti-IL-1 therapies to control autoinflammatory diseases associated with aberrant inflammasome signaling. This Review summarizes recent insights into inflammasome biology and discusses the questions that remain in the field.

Defects in MAP1S‐mediated autophagy cause reduction in mouse lifespans especially when fibronectin is overexpressed

“…It may also similarly explain the decrease in polyploidy cells in MAP1S −/− mice irrespective of LC3 overexpression. Autophagy defects lead to enhancement of oxidative stresses and promotion of inflammation and pyroptosis (Mizushima et al ., 1998; Liu et al ., 2012; Lamkanfi & Dixit, 2014). Sinusoidal dilatation is a type of vascular liver lesions previously reported to be associated with inflammatory hepatocellular adenoma (formerly known as telangiectatic focal nodular hyperplasia) (Laumonier et al ., 2008).…”

“…Autophagy defects lead to enhancement of oxidative stresses (Mizushima et al ., 1998; Liu et al ., 2012). Oxidative stress in turn activates NLRP3 inflammasome and eventually induces an inflammatory form of cell death referred to as pyroptosis that promotes the mortality and impair the survival of host structural, hematopoietic, and immune‐competent cells (Lamkanfi & Dixit, 2014; Ryter et al ., 2014; Terlizzi et al ., 2014; Yu et al ., 2014). Cancer patients with defective autophagy live a short lifespans (Jiang et al ., 2014, 2015).…”

The BCL-2 protein family, BH3-mimetics and cancer therapy

“…4 Apoptosis enables cells to be eliminated with minimal disruption to surrounding cells and is thereby distinct from necrotic cell death, which is often unregulated and results in the release of cellular debris that can prompt tissue inflammation. It is important to note that some other forms of programmed cell death, known as pyroptosis, 5 and necroptosis (also called programmed necrosis), 4,6 have risen to prominence. However, the contributions of these forms of cell death to morphogenesis during animal development, adult tissue homeostasis as well as the genesis and treatment of cancer remain to be elucidated.…”

Pathophysiology of heart failure and frailty: a common inflammatory origin?

“…In addition to membrane‐bound innate immune receptors, intracellular innate immune pathways include the inflammasome, a multiprotein complex that is activated by Nod‐like receptors (NLR) which leads to the production of IL‐1β (Chen & Nunez, 2010). The inflammasome is known to be activated by bacteria (e.g., salmonella) and viruses (e.g., influenza; Lamkanfi & Dixit, 2014). The RIG‐I‐like receptors (RLR) respond to intracellular nucleic acids in the context of viral infections (e.g., influenza virus) to produce type 1 interferons (IFN; Yoneyama et al ., 2015).…”