TNF-α and IL-10 downregulation and marked oxidative stress in Neuromyelitis Optica

Pentón‐Rol, Giselle; Cervantes‐Llanos, Majel; Martı́nez-Sánchez, Gregorio; Cabrera-Gómez, José Antonio; Valenzuela-Silva, Carmen; Ramírez‐Núñez, Omar; Casanova-Orta, Mayté; Robinson-Agramonte, María A; Lopategui-Cabezas, Ileana; López-Saura, Pedro

doi:10.1186/1476-9255-6-18

Cited by 52 publications

(40 citation statements)

References 36 publications

(32 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Simultaneously, the CSF sCD27 concentrations had a significantly positive correlation with CSF TP in NMOSD. This is consistent with the positive correlation between CSF sCD27 and proinflammatory cytokines (e.g., IL-6) [32], as well as the negative correlation between CSF sCD27 and anti-inflammatory cytokines (e.g., IL-10) [33]. Therefore, CSF sCD27 is a marker for inflammatory activity in NMOSD.…”

Section: Discussionsupporting

confidence: 68%

Cerebrospinal Fluid Level of Soluble CD27 Is Associated with Disease Severity in Neuromyelitis Optica Spectrum Disorder

Liu¹,

Zhong²,

Liu³

et al. 2018

Neuroimmunomodulation

View full text Add to dashboard Cite

Object: CD27 belongs to the tumor necrosis factor receptor family and is constitutively expressed on T cells. The concentration of cerebrospinal fluid (CSF) soluble (s)CD27 is elevated in patients with multiple sclerosis (MS). However, whether the level of CSF sCD27 is elevated in neuromyelitis optica spectrum disorder (NMOSD) remains unknown. The aim of this study was to measure the CSF concentration of sCD27 and to determine its relationship with NMOSD disease activity. Methods: CSF CXCL13 was measured by ELISA in neuromyelitis optica (NMO) (n = 31) and MS (n = 23) patients and in controls (CTLs) (n = 22). Results: The concentration of sCD27 was higher in the NMO group than in the MS (p = 0.082) and CTL (p = 0.002) groups, and there was a positive correlation with CSF IL-6 (p = 0.000) and a negative correlation with IL-10 (p = 0.073). In the NMO group, patients with higher sCD27 concentrations exhibited worse disease disability in their CSF (p = 0.006). Moreover, the sCD27 concentrations had a significantly positive correlation with the level of CSF total protein (p = 0.030). Furthermore, the patients positive for AQP4-IgG (n = 26) seemed to have higher levels of sCD27 in their CSF (p = 0.069) than those negative for AQP4-IgG (n = 5). Conclusions: We revealed that the level of CSF sCD27 was elevated in NMOSD and correlated with NMOSD disease activity.

show abstract

Section: Discussionsupporting

confidence: 68%

Cerebrospinal Fluid Level of Soluble CD27 Is Associated with Disease Severity in Neuromyelitis Optica Spectrum Disorder

Liu¹,

Zhong²,

Liu³

et al. 2018

Neuroimmunomodulation

View full text Add to dashboard Cite

show abstract

“…It is speculative that free radical oxygen chemistry may contribute to the pathogenesis in this condition [18]. Pentón-Rol et al [19] found almost undetectable levels of TNF-a, a decreased production of IL-10 and a significant up-regulation of every OS biomarker in NMO. Her results suggested that a TNF-a and IL-10 down-regulation and marked OS existed in NMO.…”

Section: Discussionmentioning

confidence: 98%

Serum uric acid levels and neuromyelitis optica

et al. 2010

View full text Add to dashboard Cite

Uric acid (UA) has been reported to be reduced in the serum of patients with multiple sclerosis (MS) and optic neuritis (ON). However, the relationship between UA and neuromyelitis optica (NMO) was unknown. NMO was claimed to be a distinct nosologic entity from MS. The aim of our study was to investigate the correlation between serum UA level and the clinical characteristics of NMO. The serum UA level was measured in 403 Chinese patients; 69 with NMO, 32 ON, 127 MS, 80 cerebral infarction (CI) patients, and 95 healthy controls (CTL). Serum UA level in NMO was significantly lower than that in CI (249.89 +/- 93.74 vs. 315.42 +/- 85.57 micromol/L, p = 0.004) and CTL (249.89 +/- 93.74 vs. 314.33 +/- 102.05 micromol/L, p < 0.0001). However, no difference was found between NMO and MS (p = 0.496) or NMO and ON (p = 0.858). When the analysis was performed in the female cohort separately, UA level was significantly lower in females than in males in all groups. It was also shown in our study that UA level in patients with NMO was not correlated with disease activity revealed by MRI, disease disability or duration of disease. Our results indicated a reduced serum UA level in patients with NMO.

show abstract

“…Previous studies suggested that reactive oxygen species may play a role in the pathogenesis of NMO. The evidence for the existence of oxygen species within inflammatory demyelinating lesions includes the presence of both lipid and protein peroxides, which involves the activation of PLA2 [40]. Therefore, the inhibition of PLA2 and the binding of NMO-IgG and AQP4 by isotetrandrine may both contribute to the inhibition of NMO.…”

Section: Discussionmentioning

confidence: 99%

Isotetrandrine Reduces Astrocyte Cytotoxicity in Neuromyelitis Optica by Blocking the Binding of NMO-IgG to Aquaporin 4

Sun

Wang

Zhou

et al. 2016

Neuroimmunomodulation

View full text Add to dashboard Cite

Objective: Neuromyelitis optica (NMO) is a severe neurological demyelinating autoimmune disease that affects the optic nerves and spinal cord with no cure and no FDA-approved therapy. Research over the last decade revealed that the binding of NMO-IgG to the water channel protein astrocyte aquaporin 4 (AQP4) might be the primary cause of NMO pathogenesis. The purpose of this study was to identify potential blockers of NMO-IgG and AQP4 binding. Methods: We developed a two-step screening platform consisting of a reporter cell-based high-throughput screen assay and a cell viability-based assay. Purified NMO-IgG from NMO patient serum and transfected Chinese hamster lung fibroblast V79 cells stably expressing human M23-AQP4 were used for primary screening of 40,000 small molecule fractions from 500 traditional Chinese herbs. Results: Thirty-six positive fractions were identified, of which 3 active fractions (at 50 μg/ml) were found to be from the same Chinese traditional herb Mahonia japonica (Thunb.). A bioactivity-guided method based on a primary screening assay for blocking activity led to the isolation of an active single natural compound, isotetrandrine, from the 3 fractions. Our immunofluorescence staining results showed that isotetrandrine can block NMO-IgG binding to AQP4 without affecting the expression and function of AQP4. It can also inhibit NMO-IgG binding to astrocyte AQP4 in NMO patient sera and block NMO-IgG-dependent complement-mediated cytotoxicity with the IC₅₀ at ∼3 μM. Conclusions: The present study developed a cell-based high-throughput screen to identify small molecule inhibitors for NMO-IgG and AQP4 binding, and suggests a potential therapeutic value of isotetrandrine in NMO.

show abstract

TNF-α and IL-10 downregulation and marked oxidative stress in Neuromyelitis Optica

Abstract: Background: Neuromyelitis optica is a central nervous system demyelinating and inflammatory syndrome. The objective of this study is to identify cytokines related to the cellular immune response as well as blood brain barrier integrity and oxidative stress.

Cited by 52 publications

References 36 publications

Cerebrospinal Fluid Level of Soluble CD27 Is Associated with Disease Severity in Neuromyelitis Optica Spectrum Disorder

Cerebrospinal Fluid Level of Soluble CD27 Is Associated with Disease Severity in Neuromyelitis Optica Spectrum Disorder

Serum uric acid levels and neuromyelitis optica

Isotetrandrine Reduces Astrocyte Cytotoxicity in Neuromyelitis Optica by Blocking the Binding of NMO-IgG to Aquaporin 4

Contact Info

Product

Resources

About