Inflammasomes in Tissue Damages and Immune Disorders After Trauma

Abstract

Trauma remains a leading cause of death worldwide. Hemorrhagic shock and direct injury to vital organs are responsible for early mortality whereas most delayed deaths are secondary to complex pathophysiological processes. These processes result from imbalanced systemic reactions to the multiple aggressions associated with trauma. Trauma results in the uncontrolled local and systemic release of endogenous mediators acting as danger signals [damage-associated molecular patterns (DAMPs)]. Their recognition by the innate immune system triggers a pro-inflammatory immune response paradoxically associated with concomitant immunosuppression. These responses, ranging in intensity from inappropriate to overwhelming, promote the propagation of injuries to remote organs, leading to multiple organ failure and death. Some of the numerous DAMPs released after trauma trigger the assembly of intracellular multiprotein complexes named inflammasomes. Once activated by a ligand, inflammasomes lead to the activation of a caspase. Activated caspases allow the release of mature forms of interleukin-1β and interleukin-18 and trigger a specific pro-inflammatory cell death termed pyroptosis. Accumulating data suggest that inflammasomes, mainly NLRP3, NLRP1, and AIM2, are involved in the generation of tissue damage and immune dysfunction after trauma. Following trauma-induced DAMP(s) recognition, inflammasomes participate in multiple ways in the development of exaggerated systemic and organ-specific inflammatory response, contributing to organ damage. Inflammasomes are involved in the innate responses to traumatic brain injury and contribute to the development of acute respiratory distress syndrome. Inflammasomes may also play a role in post-trauma immunosuppression mediated by dysregulated monocyte functions. Characterizing the involvement of inflammasomes in the pathogenesis of post-trauma syndrome is a key issue as they may be potential therapeutic targets. This review summarizes the current knowledge on the roles of inflammasomes in trauma.

Dexmedetomidine Attenuates Neuroinflammatory–Induced Apoptosis after Traumatic Brain Injury via Nrf2 signaling pathway

“…TBIinduced inflammation in the post‐TBI cerebral cortex by overexpressing TNF‐ α , IL‐1 β , and IL‐6, while DEX treatment alleviated this inflammation. NF‐ κ B is a proinflammatory regulatory cytokine that can intensify inflammatory responses . Upregulation of Nrf2 activity could improve clinical outcomes through reduction of oxidative stress and post‐traumatic inflammatory responses .…”

Annexin A1 Regulates NLRP3 Inflammasome Activation and Modifies Lipid Release Profile in Isolated Peritoneal Macrophages

“…Monocytes and macrophages express NOD-like receptors, which are very important for the immune response during inflammation [20]. By NLRP3 inflammasome activation in these cells, pro-IL-1β and pro-IL-18 are cleaved and released, increasing the pro-inflammatory response [21].…”

Involvement of Nucleotide-Binding Oligomerization Domain-Like Receptor Family Pyrin Domain Containing 3 Inflammasome in the Pathogenesis of Liver Diseases

“…The types of PRRs present in it, which define the designation of inflammasome. The PRRs can perceive the pathogen-associated molecular patterns (PAMPs) and dangerassociated molecular patterns (DAMPs), and then generate immune responses to eliminate infections and repair injured tissues (Bortolotti et al, 2018).…”