Nuclear Factor κB (NF-κB)–Mediated Inflammation in Multiple Sclerosis

Zhou, Yifan; Chu, Chun-Ping; Ma, Xiaoyu; Luo, Wenjing; Zheng, Song Guo; Qiu, Wei

doi:10.3389/fimmu.2020.00391

Cited by 77 publications

(44 citation statements)

References 129 publications

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“…The patient's sisters (monozygotic twins) were negative for the variant, and the other family members were not tested. Given the family history of glioblastoma in the patient's mother and multiple sclerosis in the maternal aunt, two conditions linked to NF-κB dysregulation (Rajaraman et al 2009;Mieczkowski et al 2015;Cartwright et al 2016;Kina et al 2019;Zhou et al 2020 Although immune-mediated bone marrow failure has not been previously reported in CVID patients, the association of NFKB1-mutated CVID with other autoimmune disorders suggests that the co-occurrence of AA and CVID in our patient was not coincidental. In fact, NFKB1 was previously found to have a critical role for maintaining a resting state of dendritic cells (DCs), induction of T cell tolerance, and CD8+ lymphocyte cytotoxicity (Dissanayake et al 2011).…”

Section: Variant Interpretationmentioning

confidence: 79%

Section: Resultsmentioning

confidence: 99%

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Aplastic anemia in a patient with CVID due to NFKB1 haploinsufficiency

Sklarz

Hurwitz

Stanley

et al. 2020

Cold Spring Harb Mol Case Stud

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Acquired aplastic anemia (AA) is a life-threatening bone marrow failure caused by an autoimmune cytotoxic T lymphocyte attack on hematopoietic stem and progenitor cells. Factors contributing to aberrant autoimmune activation in AA include a deficit of T regulatory cells and high levels of inflammatory cytokines. Several acquired conditions of immune dysregulation and genetic polymorphisms in inflammatory cytokines and human leukocyte antigen genes have been linked to an increased risk of AA. However, AA has not been reported in patients with Mendelian disorders of immune regulation. Here we report a patient with familial common variable immunodeficiency (CVID) caused by a pathogenic variant in NFKB1, who developed AA as an adult. The patient had a difficult clinical course and was unable to tolerate standard AA therapy with cyclosporine A and eltrombopag, with complications attributed in part to the effect of cyclosporine A on NF-κB signaling. Our case suggests a novel link between genetic disorders of immune regulation and AA and highlights the importance of recognizing inherited autoimmunity syndromes in AA patients for the selection of optimal therapy and prognostic counseling.

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Section: Variant Interpretationmentioning

confidence: 79%

Section: Resultsmentioning

confidence: 99%

Aplastic anemia in a patient with CVID due to NFKB1 haploinsufficiency

Sklarz

Hurwitz

Stanley

et al. 2020

Cold Spring Harb Mol Case Stud

View full text Add to dashboard Cite

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“…Therefore, elucidation of the molecular mechanisms underlying the regulation/control and resolution of inflammation is among the major topics of modern medical and veterinary sciences. Indeed, the relationship among inflammation, NF-κB signaling, and chronic diseases, including cancer [ 370 ], liver diseases [ 371 ], multiple sclerosis [ 372 ], immune-related disorders [ 69 , 373 ], and others [ 374 ], has received tremendous attention in recent years. Uncontrolled inflammation is shown to be associated with many widely occurring human diseases, including cardiovascular disease, neurodegenerative diseases, diabetes, obesity, asthma, arthritis, and periodontal diseases [ 375 ].…”

Section: Nf-κb and Inflammation In Poultry Productionmentioning

confidence: 99%

Redox Homeostasis in Poultry: Regulatory Roles of NF-κB

2021

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Redox biology is a very quickly developing area of modern biological sciences, and roles of redox homeostasis in health and disease have recently received tremendous attention. There are a range of redox pairs in the cells/tissues responsible for redox homeostasis maintenance/regulation. In general, all redox elements are interconnected and regulated by various means, including antioxidant and vitagene networks. The redox status is responsible for maintenance of cell signaling and cell stress adaptation. Physiological roles of redox homeostasis maintenance in avian species, including poultry, have received limited attention and are poorly characterized. However, for the last 5 years, this topic attracted much attention, and a range of publications covered some related aspects. In fact, transcription factor Nrf2 was shown to be a master regulator of antioxidant defenses via activation of various vitagenes and other protective molecules to maintain redox homeostasis in cells/tissues. It was shown that Nrf2 is closely related to another transcription factor, namely, NF-κB, responsible for control of inflammation; however, its roles in poultry have not yet been characterized. Therefore, the aim of this review is to describe a current view on NF-κB functioning in poultry with a specific emphasis to its nutritional modulation under various stress conditions. In particular, on the one hand, it has been shown that, in many stress conditions in poultry, NF-κB activation can lead to increased synthesis of proinflammatory cytokines leading to systemic inflammation. On the other hand, there are a range of nutrients/supplements that can downregulate NF-κB and decrease the negative consequences of stress-related disturbances in redox homeostasis. In general, vitagene–NF-κB interactions in relation to redox balance homeostasis, immunity, and gut health in poultry production await further research.

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“…Oxidative stress and inflammation are among the primary contributors to cardiovascular diseases (CVDs) such as atherosclerosis and ischemic heart failure [ 1 , 2 , 3 , 4 ]. In fact, the induction of oxidative molecules (reactive oxygen and nitrogen species) leads to the initiation of inflammatory responses and the production of inflammatory cytokines [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

Vascular Cells Proteome Associated with Bradykinin and Leptin Inflammation and Oxidative Stress Signals

et al. 2020

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Among the primary contributors to cardiovascular diseases are inflammation and oxidative imbalance within the vessel walls as well as the fibrosis of rat aortic smooth muscle cell (RASMC). Bradykinin (BK) and leptin are inflammatory modulators that are linked to vascular injury. In this study, we employed tandem LC-MS/MS to identify protein signatures that encompass protein abundance in RASMC treated with BK or leptin followed by systems biology analyses to gain insight into the biological pathways and processes linked to vascular remodeling. In the study, 1837 proteins were identified in control untreated RASMC. BK altered the expression of 72 (4%) and 120 (6.5%) proteins, whereas leptin altered the expression of 189 (10.2%) and 127 (6.5%) proteins after 24 and 48 h, respectively, compared to control RASMC. BK increased the protein abundance of leptin receptor, transforming growth factor-β. On the other hand, leptin increased the protein abundance of plasminogen activator inhibitor 1 but decreased the protein abundance of cofilin. BK and leptin induced the expression of inflammatory cytokines such as tumor necrosis factor alpha (TNF-α) and interleukin-1β (IL-1β) and pathway analysis revealed the activation of mitogen-activated protein kinases (MAPKs) and AKT pathways. The proteome profile in response to BK and leptin revealed mechanistic interplay of multiple processes that modulate inflammation and oxidative stress signals in the vasculature.

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Nuclear Factor κB (NF-κB)–Mediated Inflammation in Multiple Sclerosis

Cited by 77 publications

References 129 publications

Aplastic anemia in a patient with CVID due to NFKB1 haploinsufficiency

Aplastic anemia in a patient with CVID due to NFKB1 haploinsufficiency

Redox Homeostasis in Poultry: Regulatory Roles of NF-κB

Vascular Cells Proteome Associated with Bradykinin and Leptin Inflammation and Oxidative Stress Signals

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