Increased susceptibility of cholangiocytes to tumor necrosis factor-α cytotoxicity after bile duct ligation

2003 ◽  
Vol 285 (1) ◽  
pp. C183-C194 ◽  
Author(s):  
Gianfranco Alpini ◽  
Yoshiyuki Ueno ◽  
Laura Tadlock ◽  
Shannon S. Glaser ◽  
Gene LeSage ◽  
...  
Keyword(s):  
Bile Duct ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Actinomycin D ◽  
Bile Duct Ligation ◽  
Critical Role ◽  
Inhibition Of Proliferation ◽  
Duct Ligation ◽  
Tnf Α ◽  
Necrosis Factor

Tumor necrosis factor (TNF)-α plays a critical role in epithelial cell injury. However, the role of TNF-α in mediating cholangiocyte injury under physiological or pathophysiological conditions is unknown. Thus we assessed the effects of TNF-α alone or following sensitization by actinomycin D on cell apoptosis, proliferation, and basal and secretin-stimulated ductal secretion in cholangiocytes from normal or bile duct-ligated (BDL) rats. Cholangiocytes from normal or BDL rats were highly resistant to TNF-α alone. However, presensitization by actinomycin D increased apoptosis in cholangiocytes following BDL and was associated with an inhibition of proliferation and secretin-stimulated ductal secretion. Thus TNF-α mediates cholangiocyte injury and altered ductal secretion following bile duct ligation. These observations suggest that cholestasis may enhance susceptibility to cytokine-mediated cholangiocyte injury.

Increassed susceptibility of rat cholangiocytes to tumor necrosis factor α (TNFα) cytotoxicity following bile duct ligation

2001 ◽  
Vol 120 (5) ◽  
pp. A362
Author(s):  
Gianfranco Alpini ◽  
Laur Tadlock ◽  
Shannon Glaser ◽  
Gene Lesage ◽  
Tushar Patel
Keyword(s):  
Bile Duct ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Bile Duct Ligation ◽  
Duct Ligation ◽  
Factor Α ◽  
Necrosis Factor

scholarly journals Tumor necrosis factor-α blockade ameliorates diabetic nephropathy in rats

2019 ◽  
Author(s):  
Dongsheng Cheng ◽  
Rulian Liang ◽  
Baorui Huang ◽  
Jiasheng Hou ◽  
Jianyong Yin ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Tumor Necrosis Factor ◽  
Nlrp3 Inflammasome ◽  
Tumor Necrosis ◽  
Critical Role ◽  
Diabetic Rats ◽  
Diabetic Patients ◽  
Tubular Injury ◽  
Tnf Α ◽  
Necrosis Factor

Abstract Background Tubular injury plays a critical role in the development of diabetic nephropathy (DN), but current DN therapies do not combat tubular injury. This study was conducted to investigate if tumor necrosis factor (TNF)-α inhibition protects against tubular injury in diabetic rats and to examine the associated mechanisms. Methods Kidney biopsy tissues were collected and analyzed from 12 patients with DN and 5 control subjects. Streptozotocin (STZ)-induced diabetic rats were treated with a TNF-α inhibitor for 12 weeks. Renal function, albuminuria, histological injury, renal TNF-α messenger RNA (mRNA) and the NOD- (nucleotide-binding), LRR- (domain-like receptor) and pyrin domain-containing protein 3 (NLRP3) inflammasome were assessed. Results Diabetic patients with tubulointerstitial injury (TIN) presented with higher renal tubular expression of TNF-α mRNA and the NLRP3 inflammasome (P < 0.05). TNF-α inhibition reduced albuminuria, glomerular injury and tubular injury in STZ-induced diabetic rats (P < 0.05). Importantly, TNF-α inhibition significantly reduced the NLRP3 inflammasome in tubules (P < 0.05). Moreover, TNF-α inhibition decreased expression of tubular interleukin (IL)-6 and IL-17A mRNA. Conclusions TNF-α inhibition protects against TIN by suppressing the NLRP3 inflammasome in DN rats. Future studies may focus on the clinical protective effects of TNF-α inhibition using prospective observation.

scholarly journals Phytochemicals against TNFα-Mediated Neuroinflammatory Diseases

2020 ◽  
Vol 21 (3) ◽  
pp. 764 ◽  
Author(s):  
Lalita Subedi ◽  
Si Eun Lee ◽  
Syeda Madiha ◽  
Bhakta Prasad Gaire ◽  
Mirim Jin ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Inflammatory Responses ◽  
Inflammatory Diseases ◽  
Critical Role ◽  
Tumor Necrosis Factor Receptor ◽  
Inflammatory Disorder ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Necrosis Factor

Tumor necrosis factor-alpha (TNF-α) is a well-known pro-inflammatory cytokine responsible for the modulation of the immune system. TNF-α plays a critical role in almost every type of inflammatory disorder, including central nervous system (CNS) diseases. Although TNF-α is a well-studied component of inflammatory responses, its functioning in diverse cell types is still unclear. TNF-α functions through its two main receptors: tumor necrosis factor receptor 1 and 2 (TNFR1, TNFR2), also known as p55 and p75, respectively. Normally, the functions of soluble TNF-α-induced TNFR1 activation are reported to be pro-inflammatory and apoptotic. While TNF-α mediated TNFR2 activation has a dual role. Several synthetic drugs used as inhibitors of TNF-α for diverse inflammatory diseases possess serious adverse effects, which make patients and researchers turn their focus toward natural medicines, phytochemicals in particular. Phytochemicals targeting TNF-α can significantly improve disease conditions involving TNF-α with fewer side effects. Here, we reviewed known TNF-α inhibitors, as well as lately studied phytochemicals, with a role in inhibiting TNF-α itself, and TNF-α-mediated signaling in inflammatory diseases focusing mainly on CNS disorders.

#50 Gestational exposure of tumor necrosis factor-α (TNF-α) inhibitor drugs

2019 ◽  
Vol 88 ◽  
pp. 149-150 ◽  
Author(s):  
Erkoseoglu Ilknur ◽  
Kadioglu Mine ◽  
Cavusoglu Irem ◽  
Sisman Mulkiye ◽  
Aran Turhan ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Gestational Exposure ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor
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