NAD+-Consuming Enzymes in the Regulation of Lung Immune Responses

Legutko, Agnieszka; Lekeux, Pierre; Bureau, Fabrice

doi:10.2174/1874226200902010042

Cited by 4 publications

(5 citation statements)

References 120 publications

(142 reference statements)

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“…PARP plays an important role in the immune response of lung. [17] PARP-1 inhibitor decreased the levels of IL-6 and active plasminogen activator inhibitor 1 in the lungs, attenuated leukocyte lung transmigration, and reduced pulmonary edema and apoptosis. [18] PARP is known to have pathogenesis in mechanical VILI.…”

Section: Role Of Parp Inhibition In Acute Lung Injurymentioning

confidence: 92%

Role of poly (ADP) ribose polymerase-1 inhibition by nicotinamide as a possible additive treatment to modulate host immune response and prevention of cytokine storm in COVID-19

Gharote¹

2020

IJMS

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COVID-19 is rapidly spreading contagious disease spreading across the world. Patients at risk are elderly people and those with comorbidity. Early studies done on Chinese patients who suggest cytokine storm to be responsible for lung injury. We need to understand the mechanism of modulating such robust response of immunity and resultant cytokine storm. We suggest nicotinamide, a potential poly ADP ribose polymerase (PARP) inhibitor, as a supportive treatment for the prevention of cytokine storm from injuring the lung parenchyma. Nicotinamide supplementation albeit at high dose may modulate outcome in COVID-19. Nicotinamide was used previously to reduce ventilator-induced lung injury and lung injury due to hypoxia. Nicotinamide congeners are used to treat chronic lung disease like tuberculosis. Certainly, nicotinamide is effective pharmacotherapy in lung injury – whether acute or chronic. Other measures used in treating COVID-19 are focusing on targeting interleukin-6 – a cytokine responsible for mayhem, while few are targeting granulocyte-macrophage colony- stimulating factor. We suggest targeting PARP in addition to other measures to block cytokines. By inhibiting PARP course of COVID-19 may be altered. Understanding the pathophysiology of acute lung injury is crucial. PARP plays a pivotal role on cytokine release in response to any lung injury ranging from viral infection to hypoxia. Various antiviral defenses and immune response need to be studied in detail.

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Section: Role Of Parp Inhibition In Acute Lung Injurymentioning

confidence: 92%

Role of poly (ADP) ribose polymerase-1 inhibition by nicotinamide as a possible additive treatment to modulate host immune response and prevention of cytokine storm in COVID-19

Gharote¹

2020

IJMS

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“…NAMPT is a pleiotrophic enzyme with several different activities [ 19 ], but it is best characterized as the rate-limiting enzyme in the pathway that generates nicotinamide adenine dinucleotide (NAD+) [ 20 ]. NAD+ is a coenzyme for four families of enzymes: ADP-ribose cyclases, mono-ADP-ribosyltranferases, poly-ADP ribosyltransferases (PARPs) and the sirtuins, or type III histone deacetylases [ 21 , 22 ], and some of these enzymes have been implicated in acute lung injury models. [ 23 – 30 ].…”

Section: Introductionmentioning

confidence: 99%

Nicotinamide Exacerbates Hypoxemia in Ventilator-Induced Lung Injury Independent of Neutrophil Infiltration

et al. 2015

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BackgroundVentilator-induced lung injury is a form of acute lung injury that develops in critically ill patients on mechanical ventilation and has a high degree of mortality. Nicotinamide phosphoribosyltransferase is an enzyme that is highly upregulated in ventilator-induced lung injury and exacerbates the injury when given exogenously. Nicotinamide (vitamin B3) directly inhibits downstream pathways activated by Nicotinamide phosphoribosyltransferase and is protective in other models of acute lung injury.MethodsWe administered nicotinamide i.p. to mice undergoing mechanical ventilation with high tidal volumes to study the effects of nicotinamide on ventilator-induced lung injury. Measures of injury included oxygen saturations and bronchoalveolar lavage neutrophil counts, protein, and cytokine levels. We also measured expression of nicotinamide phosophoribosyltransferase, and its downstream effectors Sirt1 and Cebpa, Cebpb, Cebpe. We assessed the effect of nicotinamide on the production of nitric oxide during ventilator-induced lung injury. We also studied the effects of ventilator-induced lung injury in mice deficient in C/EBPε.ResultsNicotinamide treatment significantly inhibited neutrophil infiltration into the lungs during ventilator-induced lung injury, but did not affect protein leakage or cytokine production. Surprisingly, mice treated with nicotinamide developed significantly worse hypoxemia during mechanical ventilation. This effect was not linked to increases in nitric oxide production or alterations in expression of Nicotinamide phosphoribosyl transferase, Sirt1, or Cebpa and Cebpb. Cebpe mRNA levels were decreased with either nicotinamide treatment or mechanical ventilation, but mice lacking C/EBPε developed the same degree of hypoxemia and ventilator-induced lung injury as wild-type mice.ConclusionsNicotinamide treatment during VILI inhibits neutrophil infiltration of the lungs consistent with a strong anti-inflammatory effect, but paradoxically also leads to the development of significant hypoxemia. These findings suggest that pulmonary neutrophilia is not linked to hypoxemia in ventilator-induced lung injury, and that nicotinamide exacerbates hypoxemia during VILI.

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“…Even today, tracing is used in many enterprises whose production profile requires such operations. The major problem with this technology is its total dependence on the operator performing the task and its susceptibility to human errors (fatigue, oppression, routine) [15].…”

Section: Introductionmentioning

confidence: 99%

Application of optical scanning system to determine the machining allowances

2017

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Abstract. The paper contains a description of replacing a process of marking-out iron casts with 3D scanning operation and the profits it implies. It presents some of the available scanning methods which is a part of surface metrology. The paper includes a description of scanning operation using structured light method and all information necessary to perform such operation, from the equipment construction up to creation of a report for the CNC machinist.

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NAD+-Consuming Enzymes in the Regulation of Lung Immune Responses

Cited by 4 publications

References 120 publications

Role of poly (ADP) ribose polymerase-1 inhibition by nicotinamide as a possible additive treatment to modulate host immune response and prevention of cytokine storm in COVID-19

Role of poly (ADP) ribose polymerase-1 inhibition by nicotinamide as a possible additive treatment to modulate host immune response and prevention of cytokine storm in COVID-19

Nicotinamide Exacerbates Hypoxemia in Ventilator-Induced Lung Injury Independent of Neutrophil Infiltration

Application of optical scanning system to determine the machining allowances

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