Drug targets in the cytokine universe for autoimmune disease

Liu, Xuebin; Fang, Lei; Guo, Taylor B.; Mei, Hongkang; Zhang, Jingwu Z.

doi:10.1016/j.it.2012.10.003

Cited by 28 publications

(17 citation statements)

References 66 publications

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“…Inflammatory events are not specific to a single cytokine increasing at a single timepoint, instead inflammation produces dynamic regulation of many cytokines (Conti et al, 2008; Gayle, Ilyin, Miele, & Plata-Salamán, 1998; Schindler et al, 1990). Cytokines are also extremely pleiotropic (e.g ., Guzmán & Hallal-Calleros, 2010) and exhibit extensive redundancy, with many distinct proteins exerting overlapping effects (X. Liu, Fang, Guo, Mei, & Zhang, 2013).…”

Section: Introductionmentioning

confidence: 99%

Modulation of learning and memory by cytokines: Signaling mechanisms and long term consequences

Donzis

Tronson

2014

Neurobiology of Learning and Memory

227

154

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This review describes the role of cytokines and their downstream signaling cascades on the modulation of learning and memory. Immune proteins are required for many key neural processes and dysregulation of these functions by systemic inflammation can result in impairments of memory that persist long after the resolution of inflammation. Recent research has demonstrated that manipulations of individual cytokines can modulate learning, memory, and synaptic plasticity. The many conflicting findings, however, have prevented a clear understanding of the precise role of cytokines in memory. Given the complexity of inflammatory signaling, understanding its modulatory role requires a shift in focus from single cytokines to a network of cytokine interactions and elucidation of the cytokine-dependent intracellular signaling cascades. Finally, we propose that whereas signal transduction and transcription may mediate short-term modulation of memory, long-lasting cellular and molecular mechanisms such as epigenetic modifications and altered neurogenesis may be required for the long lasting impact of inflammation on memory and cognition.

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Section: Introductionmentioning

confidence: 99%

Modulation of learning and memory by cytokines: Signaling mechanisms and long term consequences

Donzis

Tronson

2014

Neurobiology of Learning and Memory

227

154

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“…The low number of pro-inflammatory cytokine will automatically reduce the anti-inflammatory cytokines. 24,25 This data was confirmed by the histopathology observation which proved that the QUE reduces the glomerulus inflammation. The effect of QUE on three steps of T cell dependent pathway of lupus pathogenesis studied can be an excellence of QUE than other compounds tested for severe lupus.…”

Section: Foxp3 + T Cells ± Sd (%)mentioning

confidence: 52%

FOXP3 Modulation of Quercetin-3-O-rhamnoside and its Impacts on Lupus Nephritis Mice

Indriyanti¹,

Soeroso²,

Khotib³

2018

JYP

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Background: Quercetin-3-O-rhamnoside (QUE) has anti-inflammatory and anti-oxidative effects which probably beneficially used in lupus. Objective: This research was focused on analyzing the effects of QUE on FOXP3 modulation to result in an anti-inflammatory outcome in the kidney of severe lupus mice. Methods: This research used Pristane-induced female BALB/c lupus mice, and the biomarkers involved in were CD4 + CD25+ T reg cells, FOXP3 T cells, anti-Sm, IL-6, and histopathology assessment of the kidney of lupus mice. The QUE group was treated and compared to the negative control which received placebo, and the positive control which received cyclophosphamide. Results: QUE increased the number of CD4 + CD25 + T reg cells (negative control: 3.01±3.43%; QUE: 18.77±5.12%; positive control: 3.26±11.09%), and FOXP3 significantly (p<0.05) (negative control: 1.14±0.54%; QUE: 2.00±1.45%; positive control: 1.73±1.14%). The antiSm level did not decrease, meanwhile the IL-6 decreased significantly, and the histopathological assessment of the kidney reveal the repairing effects of QUE on glomeruli. Conclusion: QUE has an anti-inflammatory activity which reduces the severity of lupus nephritis signs in lupus mice by initially increasing the CD4 + CD25+ and FOXP3 + Tregs numbers. QUE is potential to be further developed as a safe treatment choice for lupus nephritis. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.

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“…Li et al () introduced subtractive‐EMSA SELEX as a screening method for biomarkers in serum. Serum is a key sample for drug or biomarker discovery because it contains several proteins that are candidate targets for drug discovery, such as cytokines, endocrine factors, and other functional molecules (Liu, Fang, Guo, Mei, & Zhang, ; Pritchard, ; Siebert, Tsoukas, Robertson, & Mcinnes, ). EMSA is based on the fact that the electrophoretic mobility of a protein‐nucleic acid complex is typically lower than that of the free nucleic acid (Hellman & Fried, ).…”

Section: Aptamer Selection Using Gel Electrophoresismentioning

confidence: 99%

“…Li et al (2015) introduced subtractive-EMSA SELEX as a screening method for biomarkers in serum. Serum is a key sample for drug or biomarker discovery because it contains several proteins that are candidate targets for drug discovery, such as cytokines, endocrine factors, and other functional molecules (Liu, Fang, Guo, Mei, & Zhang, 2013;Pritchard, 2013;Siebert, Tsoukas, Robertson, & Mcinnes, 2015).…”

Section: Aptamer Selection Using Gel Electrophoresismentioning

confidence: 99%

Development of aptamers against unpurified proteins

Goto

Tsukakoshi

2017

Biotech & Bioengineering

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SELEX (Systematic Evolution of Ligands by EXponential enrichment) has been widely used for the generation of aptamers against target proteins. However, its requirement for pure target proteins remains a major problem in aptamer selection, as procedures for protein purification from crude bio-samples are not only complicated but also time and labor consuming. This is because native proteins can be found in a large number of diverse forms because of posttranslational modifications and their complicated molecular conformations. Moreover, several proteins are difficult to purify owing to their chemical fragility and/or rarity in native samples. An alternative route is the use of recombinant proteins for aptamer selection, because they are homogenous and easily purified. However, aptamers generated against recombinant proteins produced in prokaryotic cells may not interact with the same proteins expressed in eukaryotic cells because of posttranslational modifications. Moreover, to date recombinant proteins have been constructed for only a fraction of proteins expressed in the human body. Therefore, the demand for advanced SELEX methods not relying on complicated purification processes from native samples or recombinant proteins is growing. This review article describes several such techniques that allow researchers to directly develop an aptamer from various unpurified samples, such as whole cells, tissues, serum, and cell lysates. The key advantages of advanced SELEX are that it does not require a purification process from a crude bio-sample, maintains the functional states of target proteins, and facilitates the development of aptamers against unidentified and uncharacterized proteins in unpurified biological samples.

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Drug targets in the cytokine universe for autoimmune disease

Cited by 28 publications

References 66 publications

Modulation of learning and memory by cytokines: Signaling mechanisms and long term consequences

Modulation of learning and memory by cytokines: Signaling mechanisms and long term consequences

FOXP3 Modulation of Quercetin-3-O-rhamnoside and its Impacts on Lupus Nephritis Mice

Development of aptamers against unpurified proteins

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