NF-kappaB p100/p52 (Phospho-Ser872) ELISA Kit

Rheumatoid arthritis (RA) is a chronic synovial autoinflammatory disease that destructs the cartilage and bone, leading to disability. The functional regulation of major immunity-related pathways like nuclear factor kappa B (NF-kappa B), which is involved in the chronic inflammatory reactions underlying the development of RA, remains to be explored. Therefore, this study has adopted statistical and knowledge-based systemic investigations (like gene correlation, semantic similarity, and topological parameters based on graph theory) to study the gene expression status of NF-kappa B protein family (NKPF) and its regulators in synovial tissues to trace the molecular pathways through which these regulators contribute to RA. A complex protein-protein interaction map (PPIM) of 2,742 genes and 37,032 interactions was constructed from differentially expressed genes (p <= 0.05). PPIM was further decomposed into a Regulator Allied Protein Interaction Network (RA(PIN)) based on the interaction between genes (5 NKPF, 31 seeds, 131 hubs, and 652 bottlenecks). Pathway network analysis has shown the RA-specific disturbances in the functional connectivity between seed genes (RIPK1, ATG7, TLR4, TNFRSF1A, KPNA1, CFLAR, SNW1, FOSB, PARVA, CX3CL1, and TRPC6) and NKPF members (RELA, RELB, NFKB2, and REL). Interestingly, these genes are known for their involvement in inflammation and immune system (signaling by interleukins, cytokine signaling in immune system, NOD-like receptor signaling, MAPK signaling, Toll-like receptor signaling, and TNF signaling) pathways connected to RA. This study, for the first time, reports that SNW1, along with other NK regulatory genes, plays an important role in RA pathogenesis and might act as potential biomarker for RA. Additionally, these genes might play important roles in RA pathogenesis, as well as facilitate the development of effective targeted therapies. Our integrative data analysis and network-based methods could accelerate the identification of novel drug targets for RA from high-throughput genomic data.

In murine bone-marrow stromal microenvironment cells and in human multipotent mesenchymal stromal cells (MMSCs), proinflammatory cytokine interleukin-1 beta (IL-1 beta) serves as a growth factor. In murine bone tissue, IL-1 beta expression increases in vivo after irradiation. Here, we have presented our evaluation of the effects of exogenous IL-1 beta on the expression of NF-kB transcription factors in human MMSCs and stromal layer cells of murine long-term bone marrow cultures (LTBMCs). The cytokine signaling pathway was also activated in murine LTBMC by braking electron radiation in doses of 3-12 Gy. The level of expression of genes that code for IL-1 beta, IL-1 beta type-I receptor and NF-kB and IKK protein families have been studied at different time points post exposure. In both human and murine stromal cells, exogenous IL-1 beta led to an increase in the level of expression of its own gene, while levels of expression of NF-kB and IKK gene families were not substantially changed. Nevertheless, in human cells, a significant correlation between levels of expression of IL-1 beta and all NF-kB family genes was detected. It points to a similarity in IL-1 beta signal pathways in mesenchymal and hematopoietic cells, where the posttranslational modifications of NF-kB transcription factors play a major role. The irradiation of murine LTBMC resulted in a transient increase in the expression of genes that code NF-kB transcription factors and IL-1 beta. These results indicate an important role of Rel, Rela, Relb, and Nfkb2 genes in the induction of IL-1 beta signal pathway in murine stromal cells. An increase in IL-1 beta expression after the irradiation of stromal cells may be related to both the induction of inflammation due to massive cell death and to a profound stimulation of the expression of this proinflammatory cytokine expression.