Aspirin down Regulates Hepcidin by Inhibiting NF-κB and IL6/JAK2/STAT3 Pathways in BV-2 Microglial Cells Treated with Lipopolysaccharide

Li, Wanying; Li, Fei-Mi; Zhou, Yu‐Fu; Wen, Zhongmin; Ma, Juan; Ke, Ya; Qian, Zhong Ming

doi:10.3390/ijms17121921

Cited by 29 publications

(19 citation statements)

References 48 publications

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“…Experiments with cell cultures have shown that LPS induces IL-6 expression in microglia, which then induces hepcidin production in astrocytes and probably neurons [ 54 , 55 ]. LPS can induce hepcidin production in microglia as well [ 56 , 57 ], while IL-6 was shown to increase hepcidin expression in neurons through phosphorylation of STAT3 [ 55 ]. Studies with cell cultures have revealed that, in astrocytes and neurons, hepcidin induces not only FPN downregulation, but also TFR1 and DMT1 downregulation [ 58 , 59 ].…”

Section: Hepcidin Production and Action In The Brainmentioning

confidence: 99%

Hepcidin, an emerging and important player in brain iron homeostasis

Vela

2018

J Transl Med

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Hepcidin is emerging as a new important factor in brain iron homeostasis. Studies suggest that there are two sources of hepcidin in the brain; one is local and the other comes from the circulation. Little is known about the molecular mediators of local hepcidin expression, but inflammation and iron-load have been shown to induce hepcidin expression in the brain. The most important source of hepcidin in the brain are glial cells. Role of hepcidin in brain functions has been observed during neuronal iron-load and brain hemorrhage, where secretion of abundant hepcidin is related with the severity of brain damage. This damage can be reversed by blocking systemic and local hepcidin secretion. Studies have yet to unveil its role in other brain conditions, but the rationale exists, since these conditions are characterized by overexpression of the factors that stimulate brain hepcidin expression, such as inflammation, hypoxia and iron-overload.

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Section: Hepcidin Production and Action In The Brainmentioning

confidence: 99%

Hepcidin, an emerging and important player in brain iron homeostasis

Vela

2018

J Transl Med

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“…In animal models with brain inflammation and increased oxidative stress, direct and indirect suppression of local and systemic hepcidin offers neuroprotection ( Chen et al, 2015 ; Li W.-Y. et al, 2016 ; Pan et al, 2016 ; Xiong et al, 2016 ).…”

Section: The Rationale For Using Hepcidin Therapeutics In Neurodegenementioning

confidence: 99%

“…Based on the accumulating evidence about the role of inflammation on cellular iron content, it is reasonable to assume that neuroprotection can be achieved by blocking the inflammatory pathways through already established drugs. One such drug is acetylsalicylic acid, which has already been used in cultured cells to protect neuronal cells and microglia from inflammation-induced damage ( Li W.-Y. et al, 2016 ; Huang et al, 2018 ) ( Table 1 ).…”

Section: The Rationale For Using Hepcidin Therapeutics In Neurodegenementioning

confidence: 99%

The Dual Role of Hepcidin in Brain Iron Load and Inflammation

Vela

2018

Front. Neurosci.

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Hepcidin is the major regulator of systemic iron metabolism, while the role of this peptide in the brain has just recently been elucidated. Studies suggest a dual role of hepcidin in neuronal iron load and inflammation. This is important since neuronal iron load and inflammation are pathophysiological processes frequently associated with neurodegeneration. Furthermore, manipulation of hepcidin activity has recently been used to recover neuronal damage due to brain inflammation in animal models and cultured cells. Therefore, understanding the mechanistic insights of hepcidin action in the brain is important to uncover its role in treating neuronal damage in neurodegenerative diseases.

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“…Substantia nigra is rich in microglia and astroglia, which are the main actors in neuroinflammatory responses, and their double role at the interface between immune and neurophysiological responses was widely studied [30]. Previous studies demonstrated that ASA down-regulated the inflammatory condition in activated microglia induced by lipopolysaccharide (LPS) [31]. In the present study, co-administration of ASA and L-DOPA At present, this study provides the first evidence for the synergistic therapeutic strategy of ASA combined with L-DOPA in PD and LID.…”

Section: Discussionmentioning

confidence: 99%

Aspirin attenuates L-DOPA-induced dyskinesia in hemi-parkinsonian rats

Zhu¹,

Zheng²,

Li³

et al. 2020

Preprint

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Background: At present, L-DOPA remained the gold standard therapy for motor symptoms of Parkinson’s disease (PD) patients. However, prolonged administration of L-DOPA led to the development of dyskinesia. Aspirin, a non-steroidal anti-inflammatory drug (NSAID), had been widely used to relieve pain and inflammation. Recent studies indicated aspirin produced neuroprotection against dopamine (DA) neuronal loss in animal model. This study aimed to explore the effects of aspirin pre-treatment and co-treatment with L-DOPA on DA neurotoxicity and L-DOPA-induced dyskinesia (LID) as well.Methods: Rats received a single 6-hydroxydopamine (6-OHDA) injection into substantia nigra to induce DA neuronal loss. For aspirin pre-treatment before L-DOPA studies: One day after 6-OHDA stimulation, rats were daily administrated with aspirin for 3 weeks followed by daily L-DOPA treatment along with aspirin for additional 3 weeks. For aspirin co-treatment with L-DOPA studies: Three weeks after 6-OHDA administration, rats were daily treated by L-DOPA together with aspirin for another 3 weeks. DA neurotoxicity was analyzed via rat PD-like behavior test and DA neuronal counting. The movement disorders of dyskinesia triggered by L-DOPA were determined by the abnormal involuntary movements (AIM) scores analysis.Results: we demonstrated both aspirin pre-treatment and co-treatment exerted anti-LID effects during L-DOPA treatment on 6-OHDA-lesioned rats. In addition, aspirin not only ameliorated DA neuronal damage, but also reduced the development of dyskinesia without affecting L-DOPA efficacy. Furtherly, inhibition of glial cells activation and the subsequent neuroinflammatory response might be involved in aspirin-attenuated dyskinesia.Conclusion: the present study suggested aspirin could have beneficial potential to attenuate LID in PD.

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Aspirin down Regulates Hepcidin by Inhibiting NF-κB and IL6/JAK2/STAT3 Pathways in BV-2 Microglial Cells Treated with Lipopolysaccharide

Cited by 29 publications

References 48 publications

Hepcidin, an emerging and important player in brain iron homeostasis

Hepcidin, an emerging and important player in brain iron homeostasis

The Dual Role of Hepcidin in Brain Iron Load and Inflammation

Aspirin attenuates L-DOPA-induced dyskinesia in hemi-parkinsonian rats

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