Effects of MRP8, LPS, and Lenalidomide on the Expressions of TNF-<b><i>α</i></b>, Brain-Enriched, and Inflammation-Related MicroRNAs in the Primary Astrocyte Culture

Omran, Ahmed; Ashhab, Muhammad Usman; Kong, Huimin; Peng, Jing; Yin, Fei

doi:10.1155/2013/208309

Cited by 7 publications

(3 citation statements)

References 46 publications

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“…The drug induces M2 polarization of macrophages by upregulating IL-10 and activating STAT3, acting against inflammation to promote survival in MS models (Weng et al, 2018). It also downregulates inflammation-related miRNA in astrocyte cultures stimulated with LPS and MRP8 (Omran et al, 2013). Lenalidomide has also been reported to be 2,000-fold more potent than thalidomide in inhibiting TNF-α secretion from monocytes (Vallet et al, 2008).…”

Section: Current Research Surrounding Thalidomide Analogsmentioning

confidence: 99%

Neuroinflammation as a Factor of Neurodegenerative Disease: Thalidomide Analogs as Treatments

Jung

Tweedie

Scerba

et al. 2019

Front. Cell Dev. Biol.

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Neuroinflammation is initiated when glial cells, mainly microglia, are activated by threats to the neural environment, such as pathogen infiltration or neuronal injury. Although neuroinflammation serves to combat these threats and reinstate brain homeostasis, chronic inflammation can result in excessive cytokine production and cell death if the cause of inflammation remains. Overexpression of tumor necrosis factor-α (TNF-α), a proinflammatory cytokine with a central role in microglial activation, has been associated with neuronal excitotoxicity, synapse loss, and propagation of the inflammatory state. Thalidomide and its derivatives, termed immunomodulatory imide drugs (IMiDs), are a class of drugs that target the 3′-untranslated region (3′-UTR) of TNF-α mRNA, inhibiting TNF-α production. Due to their multi-potent effects, several IMiDs, including thalidomide, lenalidomide, and pomalidomide, have been repurposed as drug treatments for diseases such as multiple myeloma and psoriatic arthritis. Preclinical studies of currently marketed IMiDs, as well as novel IMiDs such as 3,6′-dithiothalidomide and adamantyl thalidomide derivatives, support the development of IMiDs as therapeutics for neurological disease. IMiDs have a competitive edge compared to similar anti-inflammatory drugs due to their blood-brain barrier permeability and high bioavailability, with the potential to alleviate symptoms of neurodegenerative disease and slow disease progression. In this review, we evaluate the role of neuroinflammation in neurodegenerative diseases, focusing specifically on the role of TNF-α in neuroinflammation, as well as appraise current research on the potential of IMiDs as treatments for neurological disorders.

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Section: Current Research Surrounding Thalidomide Analogsmentioning

confidence: 99%

Neuroinflammation as a Factor of Neurodegenerative Disease: Thalidomide Analogs as Treatments

Jung

Tweedie

Scerba

et al. 2019

Front. Cell Dev. Biol.

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“…In our previous work we found significant upregulation in these miRNAs expressions in the astrocytes stimulated with lipopolysaccharides (LPS) [28] and also in microglia exposed to oxygen glucose deprivation (OGD) [29]. Further experiments will need to prove if these miRNAs have a proinflammatory function or not in this animal model.…”

Section: Discussionmentioning

confidence: 91%

MicroRNAs expression changes in acute Streptococcus pneumoniae meningitis

Omran¹,

Jagoo

Ashhab

et al. 2014

Translational Neuroscience

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Background: Despite prompt and appropriate care, Streptococcus pneumoniae (S. pneumoniae) meningitis remains a key cause of childhood morbidity and mortality. Recently, several studies suggested the possibility of microRNAs (miRNA) involvement in multiple brain and infectious diseases. This study aimed to investigate the expressional changes of brain-enriched miRNAs (124, 134, 9, and 138), and inflammation-related miRNAs (132, 181a, 221, and 222) in the cerebral cortex of acute S. pneumoniae meningitis in postnatal day 25 rats with and without treatment. Methodology: Quantitative polymerase chain reaction (qPCR) was used to measure the expression levels of the tested brain-enriched and inflammation-related miRNAs in the cerebral cortical tissues obtained from acute experimental meningitis rat model induced by intracranial inoculation of S. pneumoniae serotype 3 with and without treatment. Control rats inoculated with saline were also included. Results: Brainenriched miRNAs are significantly downregulated in untreated animals while after treatment with antibiotic and steroid for 24 hours, miR-124 and miR-9 expressions were nearly equal to the control, while miR-134 and miR-138 were significantly upregulated. Inflammation-related miR-132 was significantly downregulated in untreated and treated animals while miRNAs (181a, 221, and 222) were significantly upregulated in untreated and treated animals. Conclusion: Acute S. pneumoniae meningitis leads to significant changes in the cerebral cortical expressions of some brain-enriched and inflammation-related miRNAs. These miRNAs may play a role in the pathogenesis of acute bacterial meningitis.

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“…To date, our group has demonstrated the differential expressions of inflammation-related and brain-enriched miRNAs in activated glias [22,30] and MTLE rat model [14] . Next we have planned to modulate the expressions of some miRNAs in rat MTLE and meningitis models to discuss its potential as a therapeutic target for CNS diseases.…”

Section: Research Highlightmentioning

confidence: 99%

Inflammation-related and Brain-enriched MicroRNAs Influence the Activation of Microglia Response to In vitro Oxygen-Glucose Deprivation

Kong¹,

Omran²,

Aly³

et al. 2014

Inflamm Cell Signal

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Microglia is one of the major resident immunecompetent cells in the central nervous system (CNS) and has become an important cellular component for understanding brain diseases. MicroRNAs (miRNAs) are small, noncoding RNAs molecules that regulate expression of protein-coding mRNAs on the post-transcriptional level; miRNAs plays important roles in microglial activation in response to brain ischemia and other stressors. Through culturing primary rat microglial cells and establishing a microglial activation model by oxygenglucose deprivation (OGD). We found that the viability of the microglia was time-dependent and expressions of inflammation-related miRNAs (miR-146a, -21, -181a, -221, and -222), and brain-enriched miRNAs (miR-124, -134, -9, -132, and -138) in microglia were modulated in an OGD model of ischemic insult. This research highlight discusses the findings of the recent study and the investigators' active research endeavors.

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Effects of MRP8, LPS, and Lenalidomide on the Expressions of TNF-α, Brain-Enriched, and Inflammation-Related MicroRNAs in the Primary Astrocyte Culture

Cited by 7 publications

References 46 publications

Neuroinflammation as a Factor of Neurodegenerative Disease: Thalidomide Analogs as Treatments

Neuroinflammation as a Factor of Neurodegenerative Disease: Thalidomide Analogs as Treatments

MicroRNAs expression changes in acute Streptococcus pneumoniae meningitis

Inflammation-related and Brain-enriched MicroRNAs Influence the Activation of Microglia Response to In vitro Oxygen-Glucose Deprivation

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