Emerging Role of Extracellular Rna in Innate Immunity, Sepsis, and Trauma

Abstract

Sepsis and trauma remain the leading causes of morbidity and mortality. Our understanding of the molecular pathogenesis in the development of multiple organ dysfunction in sepsis and trauma has evolved as more focus is on secondary injury from innate immunity, inflammation, and the potential role of endogenous danger molecules. Studies of the past several decades have generated evidence for extracellular RNAs (exRNAs) as biologically active mediators in health and disease. Here, we review studies on plasma exRNA profiling in mice and humans with sepsis and trauma, the role and mode of action by exRNAs, such as ex-micro(mi)RNAs, in host innate immune response, and their potential implications in various organ injury during sepsis and trauma.

Harnessing Extracellular microRNAs for Diagnostics and Therapeutics in Acute Systemic Inflammation

“…miRNAs regulate several aspects of the immune system, affecting the level of acute inflammation present in diseases such as sepsis [ 11 , 25 , 26 ]. Intracellular miRNAs work in their native cells to silence mRNAs and modify the post-transcriptional process, while extracellular miRNAs are transported through extracellular vesicles and other forms to execute cell–cell communication [ 12 , 27 ].…”

“…While some have argued that exosomes containing miRNAs do not maintain high enough concentrations to be physiologically relevant, others have found that the plasma contains higher concentrations of miRNAs than other RNAs [ 11 ]. In addition, there are differences when comparing the concentrations of miRNAs in the exosomes of septic individuals to those of healthy controls [ 24 ].…”

“…While first discovered as nucleic acids that remain intracellular, miRNAs have recently been found to work extracellularly as well [ 8 , 9 ]. These extracellular miRNAs can influence the activity of distant or adjacent cells and interact with other molecules in the extracellular space [ 9 , 10 , 11 ]. Overall, miRNAs serve multiple functions both intracellularly and extracellularly under physiologic and pathologic conditions [ 12 , 13 ].…”

“…Thus far, researchers have investigated the expression and activity of many species of extracellular miRNA during acute inflammation [ 11 , 12 , 20 ]. Through in vitro experiments, human blood samples, and animal models, miRNAs have demonstrated their role in immune function and consequently immune dysfunction [ 11 , 12 ].…”

“…Thus far, researchers have investigated the expression and activity of many species of extracellular miRNA during acute inflammation [ 11 , 12 , 20 ]. Through in vitro experiments, human blood samples, and animal models, miRNAs have demonstrated their role in immune function and consequently immune dysfunction [ 11 , 12 ]. Certain miRNAs can be released outside of their native cells during acute inflammation: they can be exported in exosomes, freely circulating in a protein-bound state, carried by lipoproteins, or delivered to an adjacent cell through gap junctions [ 9 , 21 , 22 , 23 ].…”