Proteomic Profiling of LPS‐Induced Macrophage‐Derived Exosomes Indicates Their Involvement in Acute Liver Injury

Wang, Guozhen; Jin, Shuguang; Ling, Xuguang; Yang, Li; Hu, Ye; Zhang, Yijie; Huang, Yun; Chen, Tingting; Lin, Jiayi; Ning, Zhu; Meng, Ying; Xu, Li

doi:10.1002/pmic.201800274

Cited by 59 publications

(49 citation statements)

References 25 publications

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“…To examine the effect of LPS treatment on human cardiomyocytes, AC16 cells were treated with increasing concentrations of LPS, which represent varying levels of bacterial infection [18][19][20]. Cell viability was measured after 48 h of LPS treatment.…”

Section: Viability Of Cardiomyocytes After Lps Treatmentmentioning

confidence: 99%

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The Role of Lipopolysaccharide-Induced Extracellular Vesicles in Cardiac Cell Death

Bell

Jones

Crenshaw

et al. 2019

Biology

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Exosomes play a crucial role in the progression of infectious diseases, as exosome release and biogenesis are affected by external factors, such as pathogenic infections. Pyrogens may aide in the progression of diseases by triggering inflammation, endothelial cell injury, and arterial plaque rupture, all of which can lead to acute coronary disease, resulting in cardiac tissue death and the onset of a cardiac event (CE). To better understand the effects of Gram-negative bacterial infections on exosome composition and biogenesis, we examined exosome characteristics after treatment of AC16 human cardiomyocytes with lipopolysaccharide (LPS), which served as a model system for Gram-negative bacterial infection. Using increasing doses (0, 0.1, 1, or 10 µg) of LPS, we showed that treatment with LPS substantially altered the composition of AC16-derived exosomes. Both the relative size and the quantity (particles/mL) of exosomes were decreased significantly at all tested concentrations of LPS treatment compared to the untreated group. In addition, LPS administration reduced the expression of exosomal proteins that are related to exosomal biogenesis. Conversely, we observed an increase in immunomodulators present after LPS administration. This evaluation of the impact of LPS on cardiac cell death and exosome composition will yield new insight into the importance of exosomes in a variety of physiological and pathological processes as it relates to disease progression, diagnosis, and treatment.

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Section: Viability Of Cardiomyocytes After Lps Treatmentmentioning

confidence: 99%

“…For control cells, exosome-free DMEM/F-12 only was used. The cells Biology 2019, 8, 69 3 of 10 and LPS were incubated for 48 hours (h) without any further manipulation [18][19][20]. The culture media was collected after 48 h.…”

mentioning

confidence: 99%

The Role of Lipopolysaccharide-Induced Extracellular Vesicles in Cardiac Cell Death

Bell

Jones

Crenshaw

et al. 2019

Biology

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“…Exosomes are small extracellular vesicles transferring molecular components such as proteins, DNA, and microRNAs (miRNAs) [43]. Exosomes represent an emerging carrier in the delivery of endogenous molecules to regulate gene expression and relevant physiological and pathophysiological processes in recipient cells [26,42,44]. Previous studies demonstrated that suppression of adrenocortical steroid synthesis by a macrophagederived product might be a new regulatory pathway in host response to LPS [45,46].…”

Section: Discussionmentioning

confidence: 99%

Triggering Receptor Expressed on Myeloid Cells-2 (TREM2) Inhibits Steroidogenesis in Adrenocortical Cell by Macrophage-derived Exosomes in Lipopolysaccharide-induced Septic Shock

Zhai

et al. 2020

Preprint

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Background: Endogenously produced glucocorticoids exhibit immunomodulating properties and are of pivotal importance for sepsis outcome. Uncontrolled activation of the immune-adrenal crosstalk increases the risk of sepsis-related death. Triggering receptor expressed on myeloid cells-2 (TREM2) is richly expressed on macrophages and has been demonstrated to improve outcome of sepsis by enhancing elimination of pathogens. However, the role and mode of action of macrophage TREM2 on adrenocortical steroidogenesis remains unclear in septic shock.Methods: The acute septic shock model was established by intraperitoneally challenging wild-type (WT) and TREM2 knock-out (Trem2-/-) mice with lipopolysaccharide (30 mg/kg). The mice were assessed for TREM2 expression and local inflammation in adrenal gland and synthesis of corticotropin releasing hormone (CRH) and adrenocorticotropic hormone (ACTH) in vivo. Bone marrow-derived macrophages or macrophage-derived exosomes were isolated from WT and Trem2-/- mice and co-cultured with adrenocortical cells. The expression of steroidogenic enzymes and corticosterone production were assessed.Results: Genetic deficiency of TREM2 caused significantly higher corticosterone levels (326.6 ± 73.0 ng/ml in Trem2-/- mice vs. 151.1 ± 58.9 ng/ml in WT mice; p < 0.001) at the early stage of LPS-induced septic shock. While TREM2 deficiency neither increased CRH and ACTH, nor exacerbated the inflammation in adrenocortical tissue during septic shock. Ex vivo study revealed that Trem2-/- macrophages significantly promoted the expression of steroidogenic enzymes and increased production of corticosterone (27.73 ± 1.78 ng/ml in Trem2-/- mice vs. 22.96 ± 1.94 ng/ml in W T mice; p < 0.01). Furthermore, Trem2-/- macrophage-derived exosomes were able to mimic Trem2-/- macrophages in enhancing adrenocortical steroidogenesis. Conclusions: At the early stage of lipopolysaccharide-induced septic shock, macrophage TREM2 inhibited the steroid synthesis and corticosterone production in adrenocortical cells, which may be partially associated with macrophage-derived exosomes.

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“…Exosomes released from LPS-treated macrophages induced NLRP3 inflammasome and caspase-1 activation of cells in vitro and in vivo, which was associated with the infiltration of macrophages and neutrophils into the tissues (28). The proteomic profiling of the exosomes showed the upregulation of exosomal proteins related with NOD-like receptor signaling pathway (28). A relevant study showed that EVs derived from Staphylococcus aureus activated NLRP3 inflammasome and caspase-1 of human macrophages, which resulted in IL-1β and IL-18 release (29).…”

Section: Nlr/inflammasome Signalingmentioning

confidence: 98%

“…Among the most characterized is NLR family pyrin domain containing 3 (NLRP3) inflammasome, which is a molecular complex known to have potential to activate caspase-1 and induce IL-1β release (27). Exosomes released from LPS-treated macrophages induced NLRP3 inflammasome and caspase-1 activation of cells in vitro and in vivo, which was associated with the infiltration of macrophages and neutrophils into the tissues (28). The proteomic profiling of the exosomes showed the upregulation of exosomal proteins related with NOD-like receptor signaling pathway (28).…”

Section: Nlr/inflammasome Signalingmentioning

confidence: 99%

Exosomes in Sepsis

et al. 2020

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Sepsis is a severe state of infection with high mortality. Pathogen-associated molecular patterns and damage-associated molecular patterns (DAMPs) initiate dysregulated systemic inflammation upon binding to pattern recognition receptors. Exosomes are endosome-derived vesicles, which carry proteins, lipids and nucleic acids, and facilitate intercellular communications. Studies have shown altered contents and function of exosomes during sepsis. In sepsis, exosomes carry increased levels of cytokines and DAMPs to induce inflammation. Exosomal DAMPs include, but are not limited to, high mobility group box 1, heat shock proteins, histones, adenosine triphosphate, and extracellular RNA. Exosomes released during sepsis have impact on multiple organs, including the lungs, kidneys, liver, cardiovascular system, and central nervous system. Here, we review the mechanisms of inflammation caused by exosomes, and their contribution to multiple organ dysfunction in sepsis.

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Proteomic Profiling of LPS‐Induced Macrophage‐Derived Exosomes Indicates Their Involvement in Acute Liver Injury

Cited by 59 publications

References 25 publications

The Role of Lipopolysaccharide-Induced Extracellular Vesicles in Cardiac Cell Death

The Role of Lipopolysaccharide-Induced Extracellular Vesicles in Cardiac Cell Death

Triggering Receptor Expressed on Myeloid Cells-2 (TREM2) Inhibits Steroidogenesis in Adrenocortical Cell by Macrophage-derived Exosomes in Lipopolysaccharide-induced Septic Shock

Exosomes in Sepsis

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