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

Abstract

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.

Individual differences in response to alcohol exposure in zebrafish (Danio rerio)

“…However, stressors cause lower HPI (hypothalamus-pituitary-interrenal) response in bold than in shy fish [ 20 , 52 , 66 , 67 ]. In terms of neurotransmitters, lower brain serotonergic activity and higher dopaminergic activity characterize proactive (bold) individuals, while reactive animals (shy) display higher serotonin and lower dopamine levels, which may also contribute to the behavioral differences in these profiles [ 20 , 52 , 66 , 68 , 69 ]. In this respect, we believe psychoactive drugs have a different effect on physiology and behavioral profiles.…”

Astrocytes in the nucleus of the solitary tract: Contributions to neural circuits controlling physiology

“…Further support for a key role of NTS astrocytes in the control of feeding comes from a series of studies on endozepines. NTS astrocytes (and tanycyte like cells of the area postrema known as vagliocytes [111] ) express octadecaneuropeptide (ODN) [112] an endozepine cleaved from acyl-CoA-binding protein (ACBP) which acts to supress food intake [113] . Delivery of ODN into the 4V supresses food intake in rats and induces c-FOS expression in the NTS [112] .…”

Paclitaxel Reduces Axonal Bclw to Initiate IP3R1-Dependent Axon Degeneration

“…Paclitaxel, a microtubule stabilizing agent commonly used to treat patients with breast, ovarian, lung, or other cancers, causes a primarily sensory neuropathy (Gornstein and Schwarz, 2014). It has been suggested that paclitaxel elicits a degenerative cascade similar to that observed after mechanical axon injury (Fukuda et al, 2017; Gornstein and Schwarz, 2014; Wang et al, 2002; Wang et al, 2004). However, the molecular mechanism for paclitaxel-induced degeneration is not understood, and there are currently no treatments available for this common disorder.…”