The role of inflammasomes in a murine model of acute respiratory distress syndrome (ARDS)

Abstract

Acute respiratory distress syndrome is rapid pulmonary inflammation that can cause organ failure which is commonly caused by sepsis, severe pneumonia and trauma. ARDS has become one of the top research priorities since the SARS-CoV-2 outbreak in 2020. From injury to damaged tissue repair, cell proliferation is a mandatory mechanistic process which is triggered by neutrophils and tissue resident macrophages releasing various factors or cytokines to restore lung homeostasis. Recent research has highlighted some important evidence that the inflammasome may be a key player in lung injury progression. Importantly, inflammasomes have been shown to have roles in microbial clearance and neutrophil recruitment as part of the host defence against bacterial or viral infections. However, the contribution of inflammasome
activation and the inflammasome-activated cytokines IL-1 beta and IL-18 in lung injury are still under deliberation. In particular, there is limited evidence of inflammasome involvement in the resolution of lung inflammation and repair. This study revealed that inflammasome proteins expressed in homeostatic and NLRP3-deficient lung tissue is not a key driver in the development of ARDS in this model. NLRP3 has a potential role in the resolution phase of lung injury because NLRP3 protein deficiency caused prolonged lung injury which was associated with increased total cell numbers in the lung on day 7 post-injury, i.e., the resolution phase in wild type mice. Caspase1 /11 (ICE) might be involved in protein leakage and recruitment or retention of cells and facilitates the initiation of the resolution stage by producing inflammatory
cytokines to recruit immune cells to the site of injury. Thus, ICE might be a contributor in lung injury but NLRP3 mediates tissue repair. Further investigation of the underlying mechanisms during the resolution phase is needed for clarification of the role of NLRP3 in injury resolution.

Date of Award	Jul 2021
Original language	English
Awarding Institution	Queen's University Belfast
Sponsors	Northern Ireland Department for the Economy
Supervisor	Yvonne Dombrowski (Supervisor), Cecilia O'Kane (Supervisor) & Denise Fitzgerald (Supervisor)