Interleukin-6: obstacles to targeting a complex cytokine in critical illness

The Lancet Respiratory Medicine, Journal Year: 2021, Volume and Issue: 9(6), P. 643 - 654

Published: April 19, 2021

Language: Английский

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Glycolytic metabolism is essential for CCR7 oligomerization and dendritic cell migration

Nature Communications, Journal Year: 2018, Volume and Issue: 9(1)

Published: June 19, 2018

Dendritic cells (DCs) are first responders of the innate immune system that integrate signals from external stimuli to direct context-specific responses. Current models suggest an active switch mitochondrial metabolism glycolysis accompanies DC activation support anabolic requirements function. We show early glycolytic is a common program for both strong and weak stimuli, but weakly activated DCs lack long-term HIF-1α-dependent reprogramming retain oxidative metabolism. Early induction associated with AKT, TBK, mTOR, sustained these pathways reprogramming. inhibition impaired maintenance elongated cell shape, motility, CCR7 oligomerization, migration draining lymph nodes. Together, our results indicate occurs independent pro-inflammatory phenotype, supports migratory ability regardless bioenergetics.

Language: Английский

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Metabolic orchestration of the wound healing response

Cell Metabolism, Journal Year: 2021, Volume and Issue: 33(9), P. 1726 - 1743

Published: Aug. 11, 2021

Language: Английский

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P2X7 receptor induces mitochondrial failure in monocytes and compromises NLRP3 inflammasome activation during sepsis

Nature Communications, Journal Year: 2019, Volume and Issue: 10(1)

Published: June 20, 2019

Abstract Sepsis is characterized by a systemic inflammatory response followed immunosuppression of the host. Metabolic defects and mitochondrial failure are common in immunocompromised patients with sepsis. The NLRP3 inflammasome important for establishing an after activation purinergic P2X7 receptor. Here, we study cohort individuals intra-abdominal origin sepsis show that patient monocytes have impaired Furthermore, most sepsis-related deaths among whose profoundly altered. In from patients, receptor associated dysfunction. results damage, which turn inhibits HIF-1α. We mortality increases mouse model when activated vivo. These data reveal molecular mechanism initiated contributes to impairment during infection.

Language: Английский

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Origin and Consequences of Necroinflammation

Physiological Reviews, Journal Year: 2018, Volume and Issue: 98(2), P. 727 - 780

Published: Feb. 21, 2018

When cells undergo necrotic cell death in either physiological or pathophysiological settings vivo, they release highly immunogenic intracellular molecules and organelles into the interstitium thereby represent strongest known trigger of immune system. With our increasing understanding necrosis as a regulated genetically determined process (RN, necrosis), necroinflammation can be pharmacologically prevented. This review discusses current knowledge about signaling pathways origin necroinflammation. Multiple RN such necroptosis, ferroptosis, pyroptosis have been evolutionary conserved most likely because their differences immunogenicity. As consequence necrosis, however, all damage associated molecular patterns (DAMPs) that extensively investigated over last two decades. Analysis allows characterizing specific signatures for each particular pathway death. While RN-pathways share DAMPs general, them actively regulate system by additional expression and/or maturation pro- anti-inflammatory cytokines/chemokines. In addition, demonstrated to modulate regeneration. For purpose better necroinflammation, we introduce novel classification this help detect relative contribution RN-pathway certain conditions.

Language: Английский

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