Inflammasome Activation: A Keystone of Proinflammatory Response in Obstructive Sleep Apnea

Díaz‐García, Elena; García-Tovar, Sara; Alfaro, Enrique; Jaureguizar, Ana; Casitas, Raquel; Sánchez-Sánchez, Begoña; Zamarrón, Ester; Fernández-Lahera, J.; López-Collazo, Eduardo; Cubillos‐Zapata, Carolina; García‐Río, Francisco

doi:10.1164/rccm.202106-1445oc

Cited by 38 publications

(33 citation statements)

References 51 publications

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“…This hypothesis was supported by other studies that showed that induction of IH promoted adipose tissue inflammation in mice [118], increased leptin expression in human adipocytes [119], and activated NLRP3-IL-1β signalling in M1 pro-inflammatory macrophages [120]. In accordance, it has been shown that obese subjects with OSAS have increased levels of leptin and higher NLRP3 activity [121,122]. Conversely, NLRP3 deficiency protected against IH in a mouse model of OSAS [123].…”

Section: Impairment Of the Nlrp3 Inflammasome In Obesity Leads To Pul...supporting

confidence: 64%

Adipose Tissue Inflammation and Pulmonary Dysfunction in Obesity

Palma

Sorice

Genchi

et al. 2022

IJMS

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Obesity is a chronic disease caused by an excess of adipose tissue that may impair health by altering the functionality of various organs, including the lungs. Excessive deposition of fat in the abdominal area can lead to abnormal positioning of the diaphragm and consequent reduction in lung volume, leading to a heightened demand for ventilation and increased exposure to respiratory diseases, such as chronic obstructive pulmonary disease, asthma, and obstructive sleep apnoea. In addition to mechanical ventilatory constraints, excess fat and ectopic deposition in visceral depots can lead to adipose tissue dysfunction, which promotes metabolic disorders. An altered adipokine-secretion profile from dysfunctional adipose tissue in morbid obesity fosters systemic, low-grade inflammation, impairing pulmonary immune response and promoting airway hyperresponsiveness. A potential target of these adipokines could be the NLRP3 inflammasome, a critical component of the innate immune system, the harmful pro-inflammatory effect of which affects both adipose and lung tissue in obesity. In this review, we will investigate the crosstalk between adipose tissue and the lung in obesity, highlighting the main inflammatory mediators and novel therapeutic targets in preventing pulmonary dysfunction.

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Section: Impairment Of the Nlrp3 Inflammasome In Obesity Leads To Pul...supporting

confidence: 64%

Adipose Tissue Inflammation and Pulmonary Dysfunction in Obesity

Palma

Sorice

Genchi

et al. 2022

IJMS

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“…IH in OSA can activate inflammatory pathways such as NF-κB, which enhanced the expression of several interleukins ( 34 , 51 ). Another pathway of HIF-1α was also reported to participants in the activation of inflammasome in monocytes under IH ( 52 ). However, it has been reported by Arnardottir et al.…”

Section: Discussionmentioning

confidence: 92%

Causal analysis between altered levels of interleukins and obstructive sleep apnea

Zhao

Fei

et al. 2022

Front. Immunol.

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BackgroundInflammation proteins including interleukins (ILs) have been reported to be related to obstructive sleep apnea (OSA). The aims of this study were to estimate the levels for several key interleukins in OSA and the causal effects between them.MethodWeighted mean difference (WMD) was used to compare the expression differences of interleukins between OSA and control, and the changed levels during OSA treatments in the meta-analysis section. A two-sample Mendelian randomization (MR) was used to estimate the causal directions and effect sizes between OSA risks and interleukins. The inverse-variance weighting (IVW) was used as the primary method followed by several other MR methods including MR Egger, Weighted median, and MR-Robust Adjusted Profile Score as sensitivity analysis.ResultsNine different interleukins—IL-1β, IL-2, IL-4, IL-6, IL-8, IL-12, IL-17, IL-18, and IL-23—were elevated in OSA compared with control to varying degrees, ranging from 0.82 to 100.14 pg/ml, and one interleukin, IL-10, was decreased by 0.77 pg/ml. Increased IL-1β, IL-6, and IL-8 rather than IL-10 can be reduced in OSA by effective treatments. Further, the MR analysis of the IVW method showed that there was no significant evidence to support the causal relationships between OSA and the nine interleukins—IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-17, and IL-18. Among them, the causal effect of OSA on IL-5 was almost significant [estimate: 0.267 (−0.030, 0.564), p = 0.078]. These results were consistent in the sensitivity analysis.ConclusionsAlthough IL-1β, IL-2, IL-4, IL-6, IL-8, IL-12, IL-17, IL-18, and IL-23 were increasing and IL-10 was reducing in OSA, no significant causal relationships were observed between them by MR analysis. Further research is needed to test the causality of OSA risk on elevated IL-5 level.

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“…Although the NLRP3 inflammasome is the master regulator of sterile inflammation [42], it has been also related with coagulation and thrombosis [43,44]. Interestingly, NLRP3dependent TF-release has been associated with several cardiovascular diseases including hypertension, ischemic cardiomyopathy, atherosclerosis, acute myocardial infarction, and acute coronary syndromes [45][46][47]. Indeed, we have found a relation between TF serum levels at admission and aSAH disease severity using the standard clinical scores.…”

Section: Discussionmentioning

confidence: 68%

NLRP3 Inflammasome Overactivation in Patients with Aneurysmal Subarachnoid Hemorrhage

Nanwani-Nanwani

García-Tovar²,

Alfaro³

et al. 2022

Transl. Stroke Res.

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Aneurysmal subarachnoid hemorrhage (aSAH) is an uncommon and severe subtype of stroke leading to the loss of many years of productive life. We analyzed NLRP3 activity as well as key components of the inflammasome cascade in monocytes and plasma from 28 patients with aSAH and 14 normal controls using flow cytometry, western blot, ELISA, and qPCR technologies. Our data reveal that monocytes from patients with aSAH present an overactivation of the NLRP3 inflammasome, which results in the presence of high plasma levels of interleukin (IL)-1β, IL-18, gasdermin D, and tissue factor. Although further research is needed, we propose that serum tissue factor concentration might be a useful prognosis biomarker for clinical outcome, and for Tako-Tsubo cardiomyopathy and cerebral vasospasm prediction. Remarkably, MCC-950 inhibitor effectively blocks NLRP3 activation in aSAH monocyte culture and supresses tissue factor release to the extracellular space. Finally, our findings suggest that NLRP3 activation could be due to the release of erythrocyte breakdown products to the subarachnoid space during aSAH event. These data define NLRP3 activation in monocytes from aSAH patients, indicating systemic inflammation that results in serum TF upregulation which in turns correlates with aSAH severity and might serve as a prognosis biomarker for aSAH clinical outcome and for cerebral vasospasm and Tako-Tsubo cardiomyopathy prediction.

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Inflammasome Activation: A Keystone of Proinflammatory Response in Obstructive Sleep Apnea

Cited by 38 publications

References 51 publications

Adipose Tissue Inflammation and Pulmonary Dysfunction in Obesity

Adipose Tissue Inflammation and Pulmonary Dysfunction in Obesity

Causal analysis between altered levels of interleukins and obstructive sleep apnea

NLRP3 Inflammasome Overactivation in Patients with Aneurysmal Subarachnoid Hemorrhage

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