Nuclear factor of activated T-cells (NFAT) regulation of IL-1β-induced retinal vascular inflammation

Giblin, Meredith J.; Smith, Taylor E.; Winkler, Garrett; Pendergrass, Hannah A.; Kim, Minjae J.; Capozzi, Megan E.; Yang, Rong; McCollum, Gary W.; Penn, John S.

doi:10.1016/j.bbadis.2021.166238

Cited by 18 publications

(13 citation statements)

References 98 publications

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“…One of the most studied cytokines is the IL-1β. MG can express IL-1β in human MG in vitro ( Giblin et al, 2021 ). Both IL-1R and IL-1R1-associated signal-transduction genes can be found in MG from NMDA-damaged mouse retinas ( Todd et al, 2019 ).…”

Section: Cytokines and The Mgmentioning

confidence: 99%

“…IL-1β induces expression of IL-6 and IL-8 in MG ( Liu et al, 2014 ; Liu et al, 2015 ), which are positively related to many retinal diseases, including but not limited to DR, AMD, central retinal vein occlusion (CRVO) ( Ghasemi, 2018 ). IL-1β has been reported to induce both TNF-α and IL-1β expression in MG, both contribute to MG inflammation ( Giblin et al, 2021 ). IL-18 is another member of the IL-1 family expressed by MG ( Zhang et al, 2022 ), well known for its pro-inflammation functions ( Kaplanski, 2018 ), and is found to participate in age-related neurodegenerative diseases with IL-1β ( Brahadeeswaran et al, 2022 ).…”

Section: Cytokines and The Mgmentioning

confidence: 99%

“…The nuclear factor of activated T-cells (NFAT) is a transcriptional regulator of inflammatory cytokines and adhesion molecules. Targeting NFAT attenuates IL-1β-induced pro-inflammatory cytokines secretion from the MG ( Giblin et al, 2021 ). HspB4/αA-crystallin, a molecular chaperone highly expressed in glial cells in the retina, regulates the stress-induced expression of pro-inflammatory cytokines in MG through the modulation of multiple key inflammatory pathways, suggesting its potential as a therapeutic target for the modulation of chronic neuroinflammation ( Nath et al, 2021 ).…”

Section: Treatment For Retinal Inflammation Through Mgmentioning

confidence: 99%

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Regulations of Retinal Inflammation: Focusing on Müller Glia

Chen

Xia

Zeng

et al. 2022

Front. Cell Dev. Biol.

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Retinal inflammation underlies multiple prevalent retinal diseases. While microglia are one of the most studied cell types regarding retinal inflammation, growing evidence shows that Müller glia play critical roles in the regulation of retinal inflammation. Müller glia express various receptors for cytokines and release cytokines to regulate inflammation. Müller glia are part of the blood-retinal barrier and interact with microglia in the inflammatory responses. The unique metabolic features of Müller glia in the retina makes them vital for retinal homeostasis maintenance, regulating retinal inflammation by lipid metabolism, purine metabolism, iron metabolism, trophic factors, and antioxidants. miRNAs in Müller glia regulate inflammatory responses via different mechanisms and potentially regulate retinal regeneration. Novel therapies are explored targeting Müller glia for inflammatory retinal diseases treatment. Here we review new findings regarding the roles of Müller glia in retinal inflammation and discuss the related novel therapies for retinal diseases.

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Section: Cytokines and The Mgmentioning

confidence: 99%

Section: Cytokines and The Mgmentioning

confidence: 99%

Section: Treatment For Retinal Inflammation Through Mgmentioning

confidence: 99%

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Regulations of Retinal Inflammation: Focusing on Müller Glia

Chen

Xia

Zeng

et al. 2022

Front. Cell Dev. Biol.

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“…In quiescent cells, NFAT exists in the cytosol in a hyperphosphorylated state. Upon challenge with an inflammatory stimulus, calcineurin dephosphorylates NFAT, causing it to shuttle to the nucleus, where it increases the transcription of inflammatory genes [56]. NFAT signaling pathways play an essential role in regulating inflammatory mediators, extracellular matrix proteins, vascular permeability, and adhesion molecules involved in the progression of atherosclerosis [57].…”

Section: Discussionmentioning

confidence: 99%

Nutrigenomic Effect of Hydroxytyrosol in Vascular Endothelial Cells: A Transcriptomic Profile Analysis

et al. 2021

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Hydroxytyrosol (HT), a peculiar olive and olive oil phenolic antioxidant, plays a significant role in the endothelial and cardiovascular protection associated with olive oil consumption. However, studies examining the effects of HT on the whole-genome expression of endothelial cells, which are prominent targets for vasculo-protective effects of olive oil polyphenols, have been lacking. This study aims to comprehensively evaluate the genomic effects exerted by HT, at the transcriptional level, in endothelial cells under resting or proinflammatory conditions. Human umbilical vein endothelial cells (HUVECs) were treated with 10 µmol/L HT for 1 h and then stimulated with 5 ng/mL interleukin (IL)-1β for 3 h. Total RNA was extracted, and gene expression profile assessed with microarray analysis. Functional enrichment analysis and pathway analysis were performed by Ingenuity Pathways Analysis. Microarray data were validated by qRT-PCR. Fixing a significance threshold at 1.5-fold change, HT affected the expression of 708 and 599 genes, respectively, in HUVECs under resting and IL-1β-stimulated conditions; among these, 190 were common to both conditions. Unfolded protein response (UPR) and endoplasmic reticulum stress resulted from the two top canonical pathways common between HT and HT-IL-1β affected genes. IL-17F/A signaling was found in the top canonical pathways of HT modified genes under resting unstimulated conditions, whereas cardiac hypertrophy signaling was identified among the pathways affected by HT-IL-1β. The transcriptomic analysis allowed pinpointing immunological, inflammatory, proliferative, and metabolic-related pathways as the most affected by HT in endothelial cells. It also revealed previously unsuspected genes and related gene pathways affected by HT, thus broadening our knowledge of its biological properties. The unbiased identification of novel genes regulated by HT improves our understanding of mechanisms by which olive oil prevents or attenuates inflammatory diseases and identifies new genes to be enquired as potential contributors to the inter-individual variation in response to functional food consumption.

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“…IL-1β certainly activates inflammatory pathways and triggers the release of other inflammatory factors from various cell types, amplifying the inflammatory pathway signals and mediating the amplification of the inflammatory damage caused by pyroptosis. For example, it stimulated chondrocytes to synthesize IL-8, TNF-α, and IL-6 ( Guerne et al., 1990 ; Lotz et al., 1992 ; Xu et al., 2021 ), promoted the expression of IL-6 and TNF-α in human retinal microvascular endothelial cells ( Giblin et al., 2021 ), and facilitated the secretion of IL-1a, IL-8, and IL-18 from fibroblast-like synoviocytes ( Kim et al., 2021 ). More importantly, IL-1β was evidenced to promote the secretion of C-C motif chemokine ligand (CCL) 20 and C-X-C motif chemokine ligand (CXCL) 10 from HPDLSCs ( Long et al., 2001 ; Zhu et al., 2012 ; Hosokawa et al., 2015 ); IL-2, IL-6, IL-8, IL-23, interferon (IFN)-γ, IL-13, and TNF-α from HPDLFs ( Abidi et al., 2020 ); and prostaglandin E2 (PGE2), IL-6, and IL-8 from HGFs ( Ono et al., 2011 ).…”

Section: Role Of Pyroptosis-regulated Cell Death Mechanisms In Period...mentioning

confidence: 99%

Pyroptosis in periodontitis: From the intricate interaction with apoptosis, NETosis, and necroptosis to the therapeutic prospects

Zhang

Xia

et al. 2022

Front. Cell. Infect. Microbiol.

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Periodontitis is highly prevalent worldwide. It is characterized by periodontal attachment and alveolar bone destruction, which not only leads to tooth loss but also results in the exacerbation of systematic diseases. As such, periodontitis has a significant negative impact on the daily lives of patients. Detailed exploration of the molecular mechanisms underlying the physiopathology of periodontitis may contribute to the development of new therapeutic strategies for periodontitis and the associated systematic diseases. Pyroptosis, as one of the inflammatory programmed cell death pathways, is implicated in the pathogenesis of periodontitis. Progress in the field of pyroptosis has greatly enhanced our understanding of its role in inflammatory diseases. This review first summarizes the mechanisms underlying the activation of pyroptosis in periodontitis and the pathological role of pyroptosis in the progression of periodontitis. Then, the crosstalk between pyroptosis with apoptosis, necroptosis, and NETosis in periodontitis is discussed. Moreover, pyroptosis, as a novel link that connects periodontitis with systemic disease, is also reviewed. Finally, the current challenges associated with pyroptosis as a potential therapeutic target for periodontitis are highlighted.

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Nuclear factor of activated T-cells (NFAT) regulation of IL-1β-induced retinal vascular inflammation

Cited by 18 publications

References 98 publications

Regulations of Retinal Inflammation: Focusing on Müller Glia

Regulations of Retinal Inflammation: Focusing on Müller Glia

Nutrigenomic Effect of Hydroxytyrosol in Vascular Endothelial Cells: A Transcriptomic Profile Analysis

Pyroptosis in periodontitis: From the intricate interaction with apoptosis, NETosis, and necroptosis to the therapeutic prospects

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