Table 1.
Summary of NF-κB expression in different types of multiple sclerosis.
| References | Participants | Methods | Samples | Main conclusions |
|---|---|---|---|---|
| Yan et al. (33) | 34 RR-MS, 20 SP-MS, 13 PP-MS, 39 HC |
WB, Immunocytochemistry, DNA-binding assay | PBMC | Compared to HC, nuclear NF-κB p65 was increased in patients with SP-MS and PP-MS; T cells from all MS subgroups and monocytes from PP-MS showed a higher nuclear p65 proportion than those from HC; the p65 DNA-binding activity in unstimulated PBMC was greater in SP-MS and PP-MS compared to HC. |
| Eggert et al. (32) | 5 RR-MS, 5 PP-MS, 10 SP-MS, 24 HC | DNA-binding assay | PBMC | The level of DNA-binding p50 in 20 MS was significantly higher than in HC but remained unchanged after therapy; the mean level of DNA-binding p65 in 20 MS was proportionate to that of HC, which decreased directly after therapy. |
| Satoh et al. (35) | 6 RR-MS | Microarray analysis | CD3+ T cells | Molecular network analysis suggested a key role of NF-κB in aberrant gene expression in T cells during MS relapse. |
| Housley et al. (34) | unclear | WB, qPCR, Immunocytochemistry, Luminex | PBMC, plasma | Naïve CD4+ cells from MS patients had higher NF-κB phospho-p65 than those from HC; MS risk variant rs228614 near NF-κB1 was associated with increased NF-κB signaling; rs1800693 in TNFR1 was associated with enhanced NF-κB responses to TNF-α and plasma cytokines. |
| Chen et al. (74) | 12 RR-MS, 7 SP-MS, 5 NMO, 9 HC | WB, Flow cytometry | PBMC, CD19+ B cells | B cells from patients with RR-MS and SP-MS exhibited a higher level of NF-κB phospho-p65 after CD40L stimulation compared with HC; after CD40L incubation, no differences in phospho-p65 were found between NMO and HC, but its basal level was much higher in NMO. |
| Hussman et al. (88) | 772 MS, 17376 HC | GWAS | Blood, cell lines, or saliva* | A large subset of MS candidate genes was found to interact in a tractable pathway regulating the NF-κB pathway, Th1/Th17 T cell infiltration, and maintenance of regulatory T cells. |
| Gveric et al. (38) | 17 MS, 6 HC | Immunocytochemistry | CNS tissue | In HC white matter, activated NF-κB p65 was found in microglial nuclei, while the c-Rel and p50 subunits and IκBα were restricted to the cytoplasm; in MS active lesions, p65, p50, and IκBα were all present in macrophage nuclei; some hypertrophic astrocytes exhibited nuclear NF-κB p65; perivascular lymphocytes showed nuclear localization of c-Rel. |
| Bonetti et al. (37) | 11 MS, 3 HC | Immunocytochemistry | CNS tissue | In HC white matter and silent MS lesions, the active form of the NF-κB p65 was negligible; up-regulated nuclear NF-κB p65 was observed in active MS lesions on a large proportion of oligodendrocytes and microglia/macrophages. |
MS, multiple sclerosis; RR-MS, relapsing-remitting MS; SP-MS, secondary progressive MS; PP-MS, primary progressive MS; NMO, neuromyelitis optica; HC, healthy controls; WB, Western Blot; PBMC, peripheral blood mononuclear cells; CNS, central nervous system.
*
DNA from most samples were extracted from venous blood, and some were extracted from cell lines or from saliva.