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

作者：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^*

来源：Cellular Immunology, 2011, 268(2): 55-59.

DOI：10.1016/j.cellimm.2011.02.007

• Tumor necrosis factor
• Nuclear factor kappa B
• Cytokine
• Chemokine
• Interleukin

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

• 出版日期2011
• 单位河北医科大学