Analysis of apoptosis-related genes in patients with clinically isolated syndrome and their association with conversion to multiple sclerosis

Hagman, Sanna; Kolasa, Marcin; Basnyat, Pabitra; Helminen, Mika; Kähönen, Mika; Dastidar, Prasun; Lehtimäki, Terho; Elovaara, Irina

doi:10.1016/j.jneuroim.2015.02.006

Cited by 14 publications

(11 citation statements)

References 27 publications

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“…Conversely, unimmunized rats with IgGs from NMO patients showed a lack of pathology and neurological dysfunction, suggesting that T cells, complements, and leukocytes participate in the pathogenesis of AQP4-Ab–mediated pathology in NMO patients (Chihara et al, 2011). Dysregulation in the cell death of T cells leads to prolonged activation of autoreactive T cells (Hagman et al, 2015). Bcl-2, which was originally identified in follicular B-cell lymphomas and localized to the cytoplasmic face of intracellular membranes (outer mitochondrial membrane, endoplasmic reticulum), inhibits apoptosis (Marsden and Strasser, 2003).…”

Section: Discussionmentioning

confidence: 99%

“…Once the cell is stimulated by agents such as TNF-α and IL-1β, NFκB1 is activated through MAP3K7 phosphorylation (DiDonato et al, 1997). TNF-α and IL-1β have the ability to transmit survival signals as Bcl-2 by activating MAP3K7/NFκB1 transcription factors (Hagman et al, 2015). In this study, both were evaluated in NMO patients (vs. HS, P < 0.001) and MS patients (vs. HS, P < 0.05).…”

Section: Discussionmentioning

confidence: 99%

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Upregulation of Bcl-2 and Its Promoter Signals in CD4+ T Cells during Neuromyelitis Optica Remission

et al. 2017

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The homeostatic balance between production and elimination of CD4+ T cells in peripheral blood plays an important role in patients with neuromyelitis optica (NMO). The objective of the present study was to evaluate the anti-apoptosis genes Bcl-2 and its promoter signal (nuclear factor kappa-light-chain-enhancer of activated B cells, NFκB) in CD4+ T cells. Healthy subjects (HS, n = 25) and patients with multiple sclerosis (MS) (n = 25) and NMO (n = 30) in remission were consecutively enrolled in this prospective study between May and December 2015. CD4+ T cells were isolated using magnetic beads coated with anti-CD4 monoclonal antibodies, and gene expression of Bcl-2, NFκB, phosphatidylinositol-4, 5-bisphosphate 3-kinase/protein kinase B (PI3K/Akt), and MAP kinase kinase kinase 7 (MAP3K7) was measured by real-time reverse transcription-polymerase chain reaction (rt-PCR). Cytokines of tumor necrosis factor (TNF)-α and interleukin (IL)-1β were detected using human cytokine multiplex assay. Bcl-2 and NFκB gene expressions were elevated in NMO patients (1.63 ± 0.25; 2.35 ± 0.25) compared with those of HS (0.90 ± 0.11; 1.42 ± 0.22) and/or MS patients (1.03 ± 0.18; 1.55 ± 0.20) (P < 0.05). MAP3K7, but not Akt, was increased in NMO patients (1.23 ± 0.18; 1.56 ± 0.22) (P < 0.01) and was a significant factor related to elevated NFκB gene expressions (P < 0.001). On the other hand, IL-1β and TNF-α were also detected in the study and the results showed that both were elevated in NMO patients (23.84 ± 1.81; 56.40 ± 2.45) (P < 0.01; P < 0.05, respectively). We propose that MAP3K7 induced by IL-1β and TNF-α but not Akt promotes NFκB expression and, in turn, prolongs Bcl-2–mediated survival of CD4+ T cells in NMO patients.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Upregulation of Bcl-2 and Its Promoter Signals in CD4+ T Cells during Neuromyelitis Optica Remission

et al. 2017

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“…More importantly, alterations in expression of these genes were identified in patients who progressed to RRMS after initially presenting with clinically isolated syndrome (CIS), suggesting that PYCARD and CASP1 may predict progression to RRMS. Most patients presenting with CIS progress to MS, suggesting a potential mechanism underlying this progression [81].…”

Section: Inflammasome Genetics and Msmentioning

confidence: 99%

Role of inflammasomes in multiple sclerosis and their potential as therapeutic targets

Govindarajan

Vaccari

Keane

2020

J Neuroinflammation

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Multiple sclerosis (MS) is a demyelinating disease of the central nervous system (CNS), and it remains the most common immune-mediated disorder affecting the CNS. While the cause of MS is unclear, the underlying pathomechanisms are thought to be either destruction by autoimmune T cells or dysfunction of myelin-producing cells. Recent advances have indicated that inflammasomes contribute the etiology of MS. Inflammasomes are multiprotein complexes of the innate immune response involved in the processing of caspase-1, the activation of pro-inflammatory cytokines interleukin (IL)-1β and IL-18 as well as the cell death-mediated mechanism of pyroptosis and the activation of the adaptive immune response. Here we review the literature to date on the role of different inflammasome signaling pathways in the pathogenesis of MS and how these pathways may be targeted to reduce deleterious inflammatory processes and improve outcomes in this patient population.

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“…Apoptosis was analyzed using a FACScan flow cytometer (BD Biosciences) and calculated using Expo32-ADC v. 1.2B software (Beckman Coulter, Inc., Brea, CA, USA). The experiment was performed according to a previous study ( 26 ).…”

Section: Methodsmentioning

confidence: 99%

Isoflurane reduces pain and inhibits apoptosis of myocardial cells through the phosphoinositide 3-kinase/protein kinaseï¿½B signaling pathway in mice during cardiac surgery

Lin

Yang

2018

Mol Med Report

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Heart bypass surgery is the most common treatment for myocardial ischemia. Clinical investigations have revealed that isoflurane anesthesia is efficient to alleviate pain during cardiac surgery, including heart bypass surgery. Previous studies have revealed the protective effects of isoflurane on myocardial cells of patients with myocardial ischemia during the perioperative period. The present study aimed to investigate the mechanism underlying the protective effects of isoflurane on myocardial cells in mice with myocardial ischemia. ELISA, flow cytometry, immunofluorescence and western blotting were used to analyze the effects of isoflurane anesthesia on myocardial cells. Briefly, myocardial cell apoptosis and viability, pain, phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) signaling pathway expression and the pharmacodynamics of isoflurane were studied in mice treated with isoflurane for heart bypass surgery. The results demonstrated that isoflurane anesthesia efficiently attenuated pain in mice during surgery. Viability and apoptosis of myocardial cells was also improved by isoflurane in vitro and in vivo. The PI3K/AKT pathway was upregulated in myocardial cells on day 3 post-operation. Mechanistically, isoflurane promoted PI3K/AKT activation, upregulated B-cell lymphoma 2 (Bcl-2)-associated X protein and Bcl-2 expression levels, and reduced the expression levels of caspase-3 and caspase-8 in myocardial cells. In conclusion, the findings indicated that isoflurane is beneficial for pain attenuation and inhibits apoptosis of myocardial cells via the PI3K/AKT signaling pathway in mice during cardiac surgery.

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Analysis of apoptosis-related genes in patients with clinically isolated syndrome and their association with conversion to multiple sclerosis

Cited by 14 publications

References 27 publications

Upregulation of Bcl-2 and Its Promoter Signals in CD4+ T Cells during Neuromyelitis Optica Remission

Upregulation of Bcl-2 and Its Promoter Signals in CD4+ T Cells during Neuromyelitis Optica Remission

Role of inflammasomes in multiple sclerosis and their potential as therapeutic targets

Isoflurane reduces pain and inhibits apoptosis of myocardial cells through the phosphoinositide 3-kinase/protein kinaseï¿½B signaling pathway in mice during cardiac surgery

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