A new target for caffeine in the developing lung: endoplasmic reticulum stress?

Rath, Philipp; Nardiello, Claudio; Morty, Rory E.

doi:10.1152/ajplung.00251.2017

Cited by 8 publications

(9 citation statements)

References 39 publications

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“…In Dayanim's study, the use of caffeine would induce the alveolar apoptosis, in contrast to Teng, Nagatomo, Jing and our results [23,[30][31][32]44]. Now, caffeine is the first line of prevention and treatment for apnea, which can reduce the severity of lung injury.…”

Section: Correlations Among Serum Caffeine Concentration a 2a R Protcontrasting

confidence: 59%

“…Caffeine is a non-selective adenosine A 1 and A 2 receptors inhibitor, which stimulate respiratory center, increase CO2 sensitivity, and enhance respiratory muscle contractility. A number of studies, such as Dayanim, Teng, Rath, and Nagatomo [23,[30][31][32], used intraperitoneal injections to reach the effective concentration in neonatal mice. In Teng's study, caffeine was reported as a non-selective phosphodiesterase inhibitor [23].…”

Section: Correlations Among Serum Caffeine Concentration a 2a R Protmentioning

confidence: 99%

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Caffeine prevents hyperoxia-induced lung injury in neonatal mice through NLRP3 inflammasome and NF-κB pathway

Chen

Zhong

et al. 2020

Respir Res

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Background: Bronchopulmonary dysplasia (BPD) is a common chronic lung disease in premature infants and hyperoxia exposure is a major cause. In hyperoxic lung injury animal model, alveolar simplification and proinflammatory cells infiltration are the main pathophysiologic changes. Caffeine is a drug used to treat apnea in premature infants. Early use of caffeine can decrease the rate and the severity of BPD while the mechanisms are still unclear. The purpose of this study was to evaluate the effects of caffeine on inflammation and lung development in neonatal mice with hyperoxic lung injury and to explore the possible mechanism. Methods: Following 14 d of 75% oxygen exposure in newborn mouse, the BPD model was established. Caffeine at a dose of 1 g/L was added in drinking water to nursing mouse. We measured the concentration of caffeine in serum and oxidative stress in lung by commercially available kits. Adenosine 2A receptor (A 2A R) expression and lung inflammation were measured by Immunohistochemistry and western blotting. Apoptosis and surfactant protein-C (SFTPC) levels were measured by immunofluorescence. The inflammasome and NF-κB pathway proteins were assessed by western blotting. Results: We found that the caffeine concentration in plasma at present dose significantly decreased the expression of A 2A R protein in mice lung. Caffeine treatment significantly reduced oxidative stress, improved weight gain, promoted alveolar development, attenuated inflammatory infiltration and lung injury in hyperoxia-induced lung injury mice. Moreover, caffeine decreased the cell apoptosis in lung tissues, especially the Type II alveolar epithelial cell. The expression of NLRP3 inflammasome protein and NF-κB pathway were significantly inhibited by caffeine treatment. Conclusion: Caffeine treatment can protect hyperoxia-induced mice lung from oxidative injury by inhibiting NLRP3 inflammasome and NF-κB pathway.

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Section: Correlations Among Serum Caffeine Concentration a 2a R Protcontrasting

confidence: 59%

Section: Correlations Among Serum Caffeine Concentration a 2a R Protmentioning

confidence: 99%

Caffeine prevents hyperoxia-induced lung injury in neonatal mice through NLRP3 inflammasome and NF-κB pathway

Chen

Zhong

et al. 2020

Respir Res

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“…It is noteworthy that intervention with an anti‐CINC‐1 antibody in a rat BPD model did limit the impact of hyperoxia on lung alveolarization, which was associated with neutrophil depletion – an observation that contrasts with the data reported here. The reasons for the conflicting conclusions are not immediately apparent and may be attributable to different BPD models (rat versus mouse), where opposite effects of pharmacological interventions to drive lung alveolarization have been noted , or may highlight CINC‐1 as a mediator of lung pathology independent of neutrophil recruitment. The data presented here suggest that neutrophils do not causally contribute to arrested lung development.…”

Section: Resultsmentioning

confidence: 99%

Resident alveolar macrophages are master regulators of arrested alveolarization in experimental bronchopulmonary dysplasia

Kalymbetova

Selvakumar

Rodríguez‐Castillo

et al. 2018

The Journal of Pathology

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Trophic functions for macrophages are emerging as key mediators of developmental processes, including bone, vessel, and mammary gland development. Yolk sac-derived macrophages mature in the distal lung shortly after birth. Myeloid-lineage macrophages are recruited to the lung and are activated under pathological conditions. These pathological conditions include bronchopulmonary dysplasia (BPD), a common complication of preterm birth characterized by stunted lung development, where the formation of alveoli is blocked. No study has addressed causal roles for immune cells in lung alveolarization. We employed antibody-based and transgenic death receptor-based depletion approaches to deplete or prevent lung recruitment of immune cell populations in a hyperoxia-based mouse model of BPD. Neither neutrophils nor exudate macrophages (which might include lung interstitial macrophages) contributed to structural perturbations to the lung that were provoked by hyperoxia; however, cells of the Csf1r-expressing monocyte/macrophage lineage were implicated as causal mediators of stunted lung development. We propose that resident alveolar macrophages differentiate into a population of CD45 CD11c SiglecF CD11b CD68 MHCII cells, which are activated by hyperoxia, and contribute to disturbances to the structural development of the immature lung. This is the first report that causally implicates immune cells in pathological disturbances to postnatal lung organogenesis. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

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“…The studies on the utility of caffeine administration to promote lung maturation described above are a case in point. A recent overview of preclinical studies on caffeine and other methylxanthines [30] reported that caffeine (or other methylxanthines) exhibited a positive effect on lung maturation or respiratory function in rats, rabbits, lambs and baboons, while in mice, caffeine either exhibited no effect at all or had a deleterious effect on lung maturation. As such, mice appear to behave differently (indeed oppositely) to all other species in terms of responses to candidate Neonatology 2020;117:233-239 DOI: 10.1159/000506989 therapies for BPD.…”

mentioning

confidence: 99%

“…Caffeine, first used to manage apnea of prematurity in the 1970s [reviewed in 27] in infants with or at risk for BPD, has been supported by multiple RCTs, starting in 2006 [28, 29]. However, studies on caffeine in experimental animal models came later, and have yielded mixed and often conflicting results [30], where caffeine administration was either protective [31] or without effect [32] or exacerbated stunting of lung development provoked by oxygen toxicity in term mouse models of BPD [33]. These diverse effects were attributed to different oxygen toxicity protocols, different mouse strains and different caffeine dosing [30].…”

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confidence: 99%

Using Experimental Models to Identify Pathogenic Pathways and Putative Disease Management Targets in Bronchopulmonary Dysplasia

Morty

2020

Neonatology

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A new target for caffeine in the developing lung: endoplasmic reticulum stress?

Cited by 8 publications

References 39 publications

Caffeine prevents hyperoxia-induced lung injury in neonatal mice through NLRP3 inflammasome and NF-κB pathway

Caffeine prevents hyperoxia-induced lung injury in neonatal mice through NLRP3 inflammasome and NF-κB pathway

Resident alveolar macrophages are master regulators of arrested alveolarization in experimental bronchopulmonary dysplasia

Using Experimental Models to Identify Pathogenic Pathways and Putative Disease Management Targets in Bronchopulmonary Dysplasia

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