Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) and receptors in type 1, type 2 and type 17 inflammation in cross-sectional asthma study

Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) reportedly promotes, or conversely, resolves inflammation in asthma. In this study of TRAIL and cell receptors in sputum, bronchoalveolar lavage and biopsy from subjects in the Severe Asthma Research Program at Wake Forest, the high TRAIL group had significant increases in all leucocytes, and was associated with increased type 1, type 2 and type 17 cytokines, but not type 9 interleukin 9. Two variants at loci in the TRAIL gene were associated with higher sputum levels of TRAIL. Increased TRAIL decoy receptor R3/DcR1 was observed on sputum leucocytes compared with death receptor R1/DR4, suggesting reduced apoptosis and prolonged cellular inflammation.

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Urinary tumour necrosis factor- excretion independently correlates with clinical markers of glomerular and tubulointerstitial injury in type 2 diabetic patients

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfl469 ◽

2006 ◽

Vol 21 (12) ◽

pp. 3428-3434 ◽

Cited By ~ 81

Author(s):

J. F. Navarro ◽

C. Mora ◽

M. Muros ◽

J. Garcia

Keyword(s):

Tumour Necrosis Factor ◽

Tumour Necrosis ◽

Diabetic Patients ◽

Clinical Markers ◽

Tubulointerstitial Injury ◽

Type 2 Diabetic Patients ◽

Type 2 Diabetic ◽

Necrosis Factor

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Association of a RING finger protein with the cytoplasmic domain of the human type-2 tumour necrosis factor receptor

Biochemical Journal ◽

10.1042/bj3090825 ◽

1995 ◽

Vol 309 (3) ◽

pp. 825-829 ◽

Cited By ~ 30

Author(s):

H Y Song ◽

D B Donner

Keyword(s):

Tumour Necrosis Factor ◽

Hybrid System ◽

Tumour Necrosis ◽

Ring Finger ◽

Tnf Receptor ◽

Intracellular Domain ◽

Two Hybrid ◽

Necrosis Factor

A human gene encoding a protein that specifically binds to the intracellular domain of the 75 kDa type-2 tumour necrosis factor (TNF) receptor (TNFR-2IC) has been identified using the yeast-based two-hybrid system. The N-terminal half of the TNF receptor-associated protein (TRAP) contains RING finger and zinc finger motifs often found in DNA-binding proteins including transcription factors. The 2.4 kb TRAP mRNA was barely detectable, if present at all, in lung, and variably expressed in heart, liver, placenta, brain, skeletal muscle, kidney and the pancreas; interestingly, the TRAP was more highly expressed in transformed cell lines than in normal tissues. This observation may be consistent with a role for this TRAP in promoting or regulating cellular proliferation. After in vitro transcription/translation and 35S labelling the TRAP was precipitated using a fusion protein consisting of glutathione S-transferase and the intracellular domain of TNFR-2 (TNFR-2IC), which showed that the two proteins directly interact in a mammalian cell-free system and also that identification of the TRAP was not an artifact of the two-hybrid system. By using truncated TNFR-2ICs for in vitro precipitation of 35S-TRAP, it was shown that the C-terminal half of the TNFR-2IC contains the domain necessary for interaction with TRAP. The TRAP identified in the present study shares considerable homology with, and may be the human homologue of, a mouse protein, TNF receptor-associated factor 2 (TRAF2), that binds mouse TNFR-2.

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Effects of tumor necrosis factor α on leptin-sensitive intestinal vagal mechanoreceptors in the cat

Canadian Journal of Physiology and Pharmacology ◽

10.1139/cjpp-2013-0025 ◽

2013 ◽

Vol 91 (11) ◽

pp. 941-950 ◽

Cited By ~ 3

Author(s):

Nathalie Quinson ◽

Véronique Vitton ◽

Michel Bouvier ◽

Jean-Charles Grimaud ◽

Anne Abysique

Keyword(s):

Tumour Necrosis ◽

Discharge Frequency ◽

Tumour Necrosis Factor Α ◽

Tnf Α ◽

Inflammatory Bowel ◽

Pre Treatment ◽

Factor Α ◽

Necrosis Factor

The involvement of tumour necrosis factor α (TNF-α) in inflammatory bowel disease (IBD) has been established, and anti-TNF-α has been suggested as a therapeutic approach for the treatment of these pathologies. We studied the effects of TNF-α on leptin-sensitive intestinal vagal units to determine whether TNF-α exerts its effects through the intestinal vagal mechanoreceptors and to investigate its interactions with substances regulating food intake. The activity of intestinal vagal mechanoreceptors was recorded via microelectrodes implanted into the nodose ganglion in anesthetized cats. TNF-α (1 μg, i.a.) increased the discharge frequency of leptin-activated units (type 1 units; P < 0.05) and had no effect on the discharge frequency of leptin-inhibited units (type 2 units). When TNF-α was administered 20 min after sulfated cholecystokinin-8 (CCK), its excitatory effects on type 1 units were significantly enhanced (P < 0.0001) and type 2 units were significantly (P < 0.05) activated. Pre-treatment with Il-1ra (250 μg, i.a.) blocked the excitatory effects of TNF-α on type 1 units whereas the excitatory effects of TNF-α administration after CCK treatment on type 2 units were not modified. The activation of leptin-sensitive units by TNF-α may explain, at least in part, the weight loss observed in IBD.

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Endothelin-2 synthesis is stimulated by the type-1 tumour necrosis factor receptor and cAMP: comparison with endothelin-converting enzyme-1 expression

Journal of Molecular Endocrinology ◽

10.1677/jme.0.0240273 ◽

2000 ◽

Vol 24 (2) ◽

pp. 273-283 ◽

Cited By ~ 6

Author(s):

GL Lambert ◽

S Barker ◽

DM Lees ◽

R Corder

Keyword(s):

Tumour Necrosis Factor ◽

Tumour Necrosis ◽

Tumour Necrosis Factor Receptor ◽

Mrna Levels ◽

Converting Enzyme ◽

Dibutyryl Camp ◽

Rt Pcr ◽

Endothelin Converting Enzyme ◽

Necrosis Factor

ABSTRACT The synthesis of the vasoconstrictor peptide endothelin-2 (ET-2) is dependent on hydrolysis of the biologically inactive intermediate big ET-2 by an endothelin-converting enzyme (ECE). Here, mechanisms inducing ET-2 synthesis have been investigated using the human renal adenocarcinoma cell line (ACHN). Synthesis of ET-2 by ACHN cells was inhibited by phosphoramidon (IC(50( congruent with11 microM). To determine whether ET-2 synthesis occurs in parallel with the metallopeptidase ECE-1, a putative processing peptidase for big ET-2, changes in the levels of their mRNAs were compared by semi-quantitative RT-PCR under conditions causing the upregulation of ET-2 synthesis. Tumour necrosis factor-alpha (TNFalpha), forskolin and a cell-permeable cAMP analogue (dibutyryl cAMP) caused concentration-dependent increases in ET-2 synthesis. Combination of forskolin or dibutyryl cAMP with TNFalpha produced a significantly greater increase in ET-2 production than these agents alone, indicating that adenylate cyclase and TNFalpha induce ET-2 synthesis by separate signalling pathways. Studies using receptor selective TNFalpha mutants, (125(I-TNFalpha binding and TNF receptor mRNA showed that type-1 TNF receptors mediate the ET-2 response to TNFalpha. PreproET-2 mRNA levels were increased by TNFalpha at 1 h and 2 h, but returned to control levels at 4 h. Treatment with forskolin significantly increased preproET-2 mRNA levels after 1 h and 4 h. ACHN cells expressed ECE-1b and ECE-1c, but not the ECE-1a isoform of this peptidase. RT-PCR for the combined isoforms ECE-1b/c/d showed TNFalpha to increase mRNA levels at 2 h and 4 h. Forskolin had no effect on ECE-1b/c/d mRNA levels. Thus, expression of ET-2 and ECE-1b/c/d mRNAs in ACHN cells do not display the co-ordinated regulation observed with typical peptide prohormone processing enzymes and their substrates.

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