Abstract |
Tumor necrosis factor receptor-associated periodic syndrome (TRAPS) is an autosomal dominant autoinflammatory condition caused by mutations in the TNFRSF1A gene which encodes the tumor necrosis factor ( TNF) receptor, TNFR1. We investigated the effect of three high penetrance and three low penetrance TNFRSF1A mutations upon NF-κB transcription factor family subunit activity, and the resulting impact upon secretion of 25 different cytokines. Whilst certain mutations resulted in elevated NF-κB p65 subunit activity, others instead resulted in elevated c-Rel subunit activity. Interestingly, high p65 activity was associated with elevated IL-8 secretion, whereas high c-Rel activity increased IL-1β and IL-12 secretion. In conclusion, while all six TNFRSF1A mutations showed enhanced NF-κB activity, different mutations stimulated distinct NF-κB family subunit activities, and this in turn resulted in the generation of unique cytokine secretory profiles.
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Authors | Belinda Nedjai, Graham A Hitman, Leigh D Church, Kirsten Minden, Margo L Whiteford, Shane McKee, Susanna Stjernberg, Tom Pettersson, Annamari Ranki, Philip N Hawkins, Peter D Arkwright, Michael F McDermott, Mark D Turner |
Journal | Cellular immunology
(Cell Immunol)
Vol. 268
Issue 2
Pg. 55-9
( 2011)
ISSN: 1090-2163 [Electronic] Netherlands |
PMID | 21420073
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | 2011 Elsevier Inc. All rights reserved. |
Chemical References |
- Cytokines
- Proto-Oncogene Proteins c-rel
- Receptors, Tumor Necrosis Factor, Type I
- TNFRSF1A protein, human
- Transcription Factor RelA
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Topics |
- Adult
- Child
- Cytokines
(immunology)
- Female
- Fever
- Hereditary Autoinflammatory Diseases
(blood, genetics, immunology)
- Humans
- Immunoassay
- Male
- Middle Aged
- Mutation
- Proto-Oncogene Proteins c-rel
(blood, immunology)
- Receptors, Tumor Necrosis Factor, Type I
(genetics, immunology)
- Signal Transduction
- Transcription Factor RelA
(blood, immunology)
- Young Adult
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