Abnormal tumor necrosis factor receptor I cell surface expression and NF-κB activation in tumor necrosis factor receptor–associated periodic syndrome

2007 ◽  
Vol 58 (1) ◽  
pp. 273-283 ◽  
Author(s):  
Belinda Nedjai ◽  
Graham A. Hitman ◽  
Nasim Yousaf ◽  
Yuti Chernajovsky ◽  
Susanna Stjernberg-Salmela ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Cell Surface ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Receptor ◽  
Surface Expression ◽  
Cell Surface Expression ◽  
Periodic Syndrome ◽  
Necrosis Factor

Metalloproteinases Are Involved in Lipopolysaccharide– and Tumor Necrosis Factor-–Mediated Regulation of CXCR1 and CXCR2 Chemokine Receptor Expression

Blood ◽  
1999 ◽  
Vol 93 (7) ◽  
pp. 2173-2185 ◽  
Author(s):  
Masud H. Khandaker ◽  
Gordon Mitchell ◽  
Luoling Xu ◽  
Joseph D. Andrews ◽  
Rajkumari Singh ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Cell Surface ◽  
Tumor Necrosis ◽  
Inflammatory Responses ◽  
Proteinase Inhibitors ◽  
Surface Expression ◽  
Receptor Expression ◽  
Cell Surface Expression ◽  
Metalloproteinase Inhibitors ◽  
Necrosis Factor

The neutrophil-specific G-protein–coupled chemokine receptors, CXCR1 and CXCR2, bind with high affinity to the potent chemoattractant interleukin-8 (IL-8). The mechanisms of IL-8 receptor regulation are not well defined, although previous studies have suggested a process of ligand-promoted internalization as a putative regulatory pathway. Herein, we provide evidence for two distinct processes of CXCR1 and CXCR2 regulation. Confocal microscopy data showed a redistribution of CXCR1 expression from the cell surface of neutrophils to internal compartments after stimulation with IL-8, whereas stimulation with bacterial lipopolysaccharide (LPS) or tumor necrosis factor- (TNF-) did not induce CXCR1 internalization but instead mediated a significant loss of membrane-proximal CXCR1 staining intensity. To investigate whether proteolytic cleavage was the mechanism responsible for LPS- and TNF-–induced downmodulation of IL-8 receptors, we tested a panel of proteinase inhibitors. The downmodulation of CXCR1 and CXCR2 by LPS and TNF- was most dramatically inhibited by metalloproteinase inhibitors; 1,10-phenanthroline and EDTA significantly attenuated LPS- and TNF-–induced loss of CXCR1 and CXCR2 cell surface expression. Metalloproteinase inhibitors also blocked the release of CXCR1 cleavage fragments into the cell supernatants of LPS- and TNF-–stimulated neutrophils. In addition, while treatment of neutrophils with LPS and TNF- inhibited IL-8 receptor–mediated calcium mobilization and IL-8–directed neutrophil chemotaxis, both 1,10-phenanthroline and EDTA blocked these inhibitory processes. In contrast, metalloproteinase inhibitors did not affect IL-8–mediated downmodulation of CXCR1 and CXCR2 cell surface expression or receptor signaling. Thus, these findings may provide further insight into the mechanisms of leukocyte regulation during immunologic and inflammatory responses.

scholarly journals Fas and tumor necrosis factor receptor-mediated cell death: similarities and distinctions.

1994 ◽  
Vol 180 (2) ◽  
pp. 557-567 ◽  
Author(s):  
M V Clement ◽  
I Stamenkovic
Keyword(s):  
Cell Death ◽  
Tumor Necrosis Factor ◽  
Fusion Proteins ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Receptor ◽  
Cd40 Ligand ◽  
Surface Expression ◽  
Cell Surface Expression ◽  
Intermediate Cell ◽  
Necrosis Factor

Fas antigen and two tumor necrosis factor receptors (TNFR), p55 and p75, are implicated in the triggering of cell death upon stimulation by natural ligands and specific monoclonal antibodies. However, the relative efficiency of each receptor, the mechanisms that regulate their function and the signaling pathways they employ, remain to be elucidated. In this study, fusion proteins, composed of the extracellular domain of CD40 and the intracellular and transmembrane domains of Fas, TNFRp55 and TNFRp75, were stably expressed in a human melanoma cell line that is deficient in Fas and TNFR expression. Transfectants were stimulated by a soluble recombinant form of the CD40 ligand gp39, and the effect on cell viability determined. Engagement of all three fusion proteins by the gp39 ligand induced lethal signals, but the rate at which cell death occurred was distinct. Fas-derived signals were observed to have the most rapid effect, killing most cells within hours of stimulation, whereas TNFRp55- and TNFRp75-associated signals resulted in cell death within 2-3 d after engagement by ligand. It is interesting to note that optimal cell killing by all three fusion proteins was dependent on a critical, low to intermediate, cell surface expression level. High levels of fusion protein expression, on the other hand, were associated with inhibition of cell death. Our results provide a model to study Fas and TNFR-mediated cell death and suggest a novel mechanism for the regulation of death signals triggered by members of the TNFR family.

Tumor necrosis factor alpha leads to increased cell surface expression of CXCR4 in SK-N-MC cells

2005 ◽  
Vol 11 (3) ◽  
pp. 247-255 ◽  
Author(s):  
Kevin Rostasy ◽  
Gullue Gorgun ◽  
Yelena Kleyner ◽  
Anthony Garcia ◽  
Michael Kramer ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Cell Surface ◽  
Tumor Necrosis Factor Alpha ◽  
Tumor Necrosis ◽  
Surface Expression ◽  
Cell Surface Expression ◽  
Necrosis Factor Alpha ◽  
Factor Alpha ◽  
Necrosis Factor
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