Inflammasome activation in acute lung injury

Author:

McVey Mark J.123,Steinberg Benjamin E.124,Goldenberg Neil M.124

Affiliation:

1. Department of Anesthesiology and Pain Medicine, University of Toronto, Toronto, Ontario, Canada

2. Department of Anesthesia and Pain Medicine, Hospital for Sick Children, Toronto, Ontario, Canada

3. Department of Physics, Ryerson University, Toronto, Ontario, Canada

4. Department of Physiology, University of Toronto, Toronto, Ontario, Canada

Abstract

Inflammasomes are multiprotein complexes tasked with sensing endogenous or exogenous inflammatory signals and integrating this signal into a downstream response. Inflammasome activation has been implicated in a variety of pulmonary diseases, including pulmonary hypertension, bacterial pneumonia, COPD, and asthma. Of increasing interest is the contribution of inflammasome activation in the context of acute lung injury/acute respiratory distress syndrome (ALI/ARDS). Inflammasome activation in both the lung parenchyma and resident immune cells generates intereukin-1β (IL-1β) and IL-18, both of which drive the cascade of lung inflammation forward. Blockade of these responses has been shown to be beneficial in animal models and is a focus of translational research in the field. In this review, we will discuss the assembly and regulation of inflammasomes during lung inflammation, highlighting therapeutically viable effector steps. We will examine the importance of IL-1β and IL-18, two key products of inflammasome activation, in ALI, as well as the contribution of the pulmonary endothelial cell to this process. Finally, we will explore translational research moving toward anti-inflammasome therapies for ALI/ARDS and speculate toward future directions for the field.

Funder

International Anesthesia Research Society

Ontario Thoracic Society

Canadian Lung Association

Gouvernement du Canada | CIHR | Institute of Health Services and Policy Research

Publisher

American Physiological Society

Subject

Cell Biology,Physiology (medical),Pulmonary and Respiratory Medicine,Physiology

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