scholarly journals Reprogramming mitochondrial metabolism in macrophages as an anti-inflammatory signal

2016 ◽  
Vol 46 (1) ◽  
pp. 13-21 ◽  
Author(s):  
Evanna L. Mills ◽  
Luke A. O'Neill
Keyword(s):  
Mitochondrial Metabolism ◽  
Anti Inflammatory

Hypoxia-inducible factors individually facilitate inflammatory myeloid metabolism and inefficient cardiac repair

2021 ◽  
Vol 218 (9) ◽  
Author(s):  
Matthew DeBerge ◽  
Connor Lantz ◽  
Shirley Dehn ◽  
David P. Sullivan ◽  
Anja M. van der Laan ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Tissue Repair ◽  
Myeloid Cell ◽  
Selective Inhibition ◽  
Mitochondrial Metabolism ◽  
Hypoxia Inducible Factors ◽  
Low Oxygen ◽  
Ischemic Tissue ◽  
Anti Inflammatory ◽  
Parenchymal Cells

Hypoxia-inducible factors (HIFs) are activated in parenchymal cells in response to low oxygen and as such have been proposed as therapeutic targets during hypoxic insult, including myocardial infarction (MI). HIFs are also activated within macrophages, which orchestrate the tissue repair response. Although isoform-specific therapeutics are in development for cardiac ischemic injury, surprisingly, the unique role of myeloid HIFs, and particularly HIF-2α, is unknown. Using a murine model of myocardial infarction and mice with conditional genetic loss and gain of function, we uncovered unique proinflammatory roles for myeloid cell expression of HIF-1α and HIF-2α during MI. We found that HIF-2α suppressed anti-inflammatory macrophage mitochondrial metabolism, while HIF-1α promoted cleavage of cardioprotective MerTK through glycolytic reprogramming of macrophages. Unexpectedly, combinatorial loss of both myeloid HIF-1α and HIF-2α was catastrophic and led to macrophage necroptosis, impaired fibrogenesis, and cardiac rupture. These findings support a strategy for selective inhibition of macrophage HIF isoforms and promotion of anti-inflammatory mitochondrial metabolism during ischemic tissue repair.

scholarly journals Lactate Arterial-Central Venous Gradient among COVID-19 Patients in ICU: A Potential Tool in the Clinical Practice

2020 ◽  
Vol 2020 ◽  
pp. 1-5
Author(s):  
Giuseppe Nardi ◽  
Gianfranco Sanson ◽  
Lucia Tassinari ◽  
Giovanna Guiotto ◽  
Antonella Potalivo ◽  
...  
Keyword(s):  
Blood Lactate ◽  
Venous Blood ◽  
Lactate Concentration ◽  
Blood Lactate Concentration ◽  
Mitochondrial Metabolism ◽  
Lung Cells ◽  
Central Venous ◽  
Central Venous Blood ◽  
Arterial Blood ◽  
Anti Inflammatory

Objective. In physiological conditions, arterial blood lactate concentration is equal to or lower than central venous blood lactate concentration. A reversal in this rate (i.e., higher lactate concentration in central venous blood), which could reflect a derangement in the mitochondrial metabolism of lung cells induced by inflammation, has been previously reported in patients with ARDS but has been never explored in COVID-19 patients. The aim of this study was to explore if the COVID-19-induced lung cell damage was mirrored by an arterial lactatemia higher than the central venous one; then if the administration of anti-inflammatory therapy (i.e., canakinumab 300 mg subcutaneous) could normalize such abnormal lactate a-cv difference. Methods. A prospective cohort study was conducted, started on March 25, 2020, for a duration of 10 days, enrolling 21 patients affected by severe COVID-19 pneumonia undergoing mechanical ventilation consecutively admitted to the ICU of the Rimini Hospital, Italy. Arterial and central venous blood samples were contemporarily collected to calculate the difference between arterial and central venous lactate (Delta a-cv lactate) concentrations within 24 h from tracheal intubation (T0) and 24 hours after canakinumab administration (T1). Results. At T0, 19 of 21 (90.5%) patients showed a pathologic Delta a-cv lactate (median 0.15 mmol/L; IQR 0.07–0.25). In the 13 patients undergoing canakinumab administration, at T1, Delta a-cv lactate decreased in 92.3% of cases, the decrease being statistically significant (T0: median 0.24, IQR 0.09–0.31 mmol/L; T1: median −0.01, IQR −0.08–0.04 mmol/L; p=0.002). Conclusion. A reversed Delta a-cv lactate might be interpreted as one of the effects of COVID-19-related cytokine storm, which could reflect a derangement in the mitochondrial metabolism of lung cells induced by severe inflammation or other uncoupling mediators. In addition, Delta a-cv lactate decrease might also reflect the anti-inflammatory activity of canakinumab. Our preliminary findings need to be confirmed by larger outcome studies.

758: Inflammatory and Anti-Inflammatory Regulators alter Levels of an Inhibitor of Apoptosis (IAP), Survivin, in T-24 Bladder Cancer Cells

2007 ◽  
Vol 177 (4S) ◽  
pp. 254-254
Author(s):  
Justin J. Cohen ◽  
Bayan T. Takizawa ◽  
Hristos Z. Kaimkliotis ◽  
David J. Rosenberg ◽  
Marcia A. Wheeler ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cancer Cells ◽  
Inhibitor Of Apoptosis ◽  
Bladder Cancer Cells ◽  
Anti Inflammatory

1216: Oral Treatment with a Vitamin D3 Analogue Shows Anti Inflammatory Effects and Reduces Bladder Overactivity in Rodent Models of Chronic Cystitis

2005 ◽  
Vol 173 (4S) ◽  
pp. 330-330
Author(s):  
Peter Zvara ◽  
Fabio Benigni ◽  
Enrico Baroni ◽  
Marija Zecevic ◽  
Antonia Monno ◽  
...  
Keyword(s):  
Vitamin D3 ◽  
Oral Treatment ◽  
Rodent Models ◽  
Chronic Cystitis ◽  
Anti Inflammatory
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