Differential cytokine secretion results from p65 and c-Rel NF-IoB subunit signaling in peripheral blood mononuclear cells of TNF receptor-associated periodic syndrome patients

• Published in: Cellular immunology 2011-01, Vol.268 (2), p.55-59
• Main Authors: Nedjai, Belinda, Hitman, Graham A, Church, Leigh D, Minden, Kirsten, Whiteford, Margo L, McKee, Shane, Stjernberg, Susanna, Pettersson, Tom, Ranki, Annamari, Hawkins, Philip N, Arkwright, Peter D, McDermott, Michael F, Turner, Mark D
• Format: Article
• Language: English
• ISSN: 0008-8749
• DOI: 10.1016/j.cellimm.2011.02.007

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-IoB transcription factor family subunit activity, and the resulting impact upon secretion of 25 different cytokines. Whilst certain mutations resulted in elevated NF-IoB 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-1I2 and IL-12 secretion. In conclusion, while all six TNFRSF1A mutations showed enhanced NF-IoB activity, different mutations stimulated distinct NF-IoB family subunit activities, and this in turn resulted in the generation of unique cytokine secretory profiles.