Mouse anti-Human TNFSF10 monoclonal antibody, clone SJL-3.2 [PE]

OBJECTIVES: Ankylosing spondylitis (AS) is a chronic, inflammatory arthritis and autoimmune disease. BACKGROUND: The main symptom of AS is inflammatory spinal pain; with time, some patients develop ankylosis and spinal immobility. We aim to find cure available for ankylosing spondylitis. MATERIALS AND METHODS: We used the GSE11886 series to identify potential genes that related to AS to construct a regulation network. RESULTS: In the network, some of TFs and target genes have been proved related with AS in previous study, such as NFKB1, STAT1, STAT4, TNFSF10, IL2RA, and IL2RB. We also found some newTFs (Franscription Factors) and target genes response to AS, such as BXDC5, and EGFR. Further analysis indicated some significant pathways are associated with AS, including antigen processing and presentation and cytokine-cytokine receptor interaction, etc.; although not significant, there was evident that they play an important role in AS progression, such as apoptosis and systemic lupus erythematosus. CONCLUSIONS: Therefore, it is demonstrated that transcriptome network analysis is useful in identification of the candidate genes in AS.

Elevated expression of E2F1 in adipocyte fraction of human visceral adipose tissue (hVAT) associates with a poor cardiometabolic profile. We hypothesized that beyond directly activating autophagy and MAP3K5 (ASK)-MAP kinase signaling, E2F1 governs a distinct transcriptome that contributes to adipose tissue and metabolic dysfunction in obesity. We performed RNA sequencing of hVAT samples from age-, sex-, and BMI-matched patients, all obese, whose visceral E2F1 protein expression was either high (E2F1(high)) or low (E2F1(low)). Tumor necrosis factor superfamily (TNFSF) members, includingTRAIL(TNFSF10),TL1A(TNFSF15), and their receptors, were enriched in E2F1(high). WhileTRAILwas equally expressed in adipocytes and stromal vascular fraction (SVF),TL1Awas mainly expressed in SVF, and TRAIL-inducedTL1Awas attributed to CD4(+)and CD8(+)subclasses of hVAT T cells. In human adipocytes, TL1A enhanced basal and impaired insulin-inhibitable lipolysis and altered adipokine secretion, and in human macrophages it induced foam cell biogenesis and M1 polarization. Two independent human cohorts confirmed associations between TL1A and TRAIL expression in hVAT and higher leptin and IL6 serum concentrations, diabetes status, and hVAT-macrophage lipid content. Jointly, we propose an intra-adipose tissue E2F1-associated TNFSF paracrine loop engaging lymphocytes, macrophages, and adipocytes, ultimately contributing to adipose tissue dysfunction in obesity.