BACKGROUND Tumor necrosis factor-α has been proven an effective anticancer agent in preclinical studies. However, the translation of TNFα from research to clinic has been blocked by significant systemic toxicity and limited efficacy at maximal tolerated dose, which need urgently to be solved. METHODS The level of cytosolic Ca2+ was assessed by Fura-2 in HCC cells. After changing cytosolic Ca2...

Neuroinflammation is a hallmark of Alzheimer's disease and TNFα as the main inducer of neuroinflammation has neurodegenerative but also pro-regenerative properties, however, the dose-dependent molecular changes on signaling pathway level are not fully understood. We performed quantitative proteomics and phospho-proteomics to target this point.In HT22 cells, we found that TNFα reduced mitochondr...

TNFα has been identified as playing an important role in pathologic complications associated with diabetic retinopathy and retinal inflammation, such as retinal leukostasis. However, the transcriptional effects of TNFα on retinal microvascular endothelial cells and the different signaling pathways involved are not yet fully understood. In the present study, RNA-seq was used to profile the trans...

The proinflammatory cytokine TNFα contributes to cell death in central nervous system (CNS) disorders by altering synaptic neurotransmission. TNFα contributes to excitotoxicity by increasing GluA2-lacking AMPA receptor (AMPAR) trafficking to the neuronal plasma membrane. In vitro, increased AMPAR on the neuronal surface after TNFα exposure is associated with a rapid internalization of GABA(A) r...

There is no consensus on whether it is safe to re-administer tumor necrosis factor-alpha (TNFα) inhibitors in patients with rheumatoid arthritis (RA) or ankylosing spondylitis (AS) flared after withdrawal of TNFα inhibitors due to active tuberculosis (TB). We evaluated the safety of restarting anti-TNFα therapy in patients with TNFα-associated TB. We used data of 1,012 patients with RA or AS tr...

The objective of this study was to determine the role of individual NFAT isoforms in TNFα-induced retinal leukostasis. To this end, human retinal microvascular endothelial cells (HRMEC) transfected with siRNA targeting individual NFAT isoforms were treated with TNFα, and qRT-PCR was used to examine the contribution of each isoform to the TNFα-induced upregulation of leukocyte adhesion proteins....

Inflammatory bowel disease (Crohn's disease (CD) and ulcerative colitis (UC)) is a multifactorial disease resulting from immune dysregulation in the gut. The underlying colitis is characterized by high levels of inflammatory cytokines, including TNFα. Biological intervention for IBD patients using anti-TNFα antibodies is often an effective therapeutic solution. However, TNFα neutralization fail...

Gene transcription is regulated by post-translation modifications. Histone deacetylases (HDACs) remove acetyl groups from histone and non-histone factors inhibiting transcription. Proinflammatory cytokines such as TNFα activate the canonical nuclear factor-κB (NF-κB) pathway. Earlier we established a cytoprotective role for NF-κB in the heart. Though a causal relationship for HDAC1 and NF-κB ha...

Objective: Limited information exists on real-world use of anti-tumor necrosis factor-α (TNFα) biologic agents in ankylosing spondylitis (AS). This study evaluated the treatment patterns and costs of anti-TNFα biologic therapy and disease-modifying antirheumatic drugs (DMARDs) in patients with AS. Methods: MarketScan claim databases were used to identify anti-TNFα biologic treatment-naïve AS pa...