A role for transcription factor NF-κB in autoimmunity: possible interactions of genes, sex, and the immune response

Abstract

Sex hormones have long been implicated in autoimmune diseases because women account for 80% of cases. The mechanism of hormonal action in autoimmunity is unknown. Drawing on genetic studies of autoimmune disease, this article discusses how both genes and sex hormones may exert their effects through the same general mechanism, dysregulation of transcription factor NF-kappaB, an immunoregulatory protein. Gene and hormone alterations of the NF-kappaB signaling cascade provide a unifying hypothesis to explain the wide-ranging human and murine autoimmune disease phenotypes regulated by NF-kappaB, including cytokine balance, antigen presentation, lymphoid development, and lymphoid repertoire selection by apoptosis.

Sex‐Specific Genetic Variants are Associated With Coronary Endothelial Dysfunction

“…Errors in genes encoding inflammatory or anti‐inflammatory molecules are candidates for increasing risk of developing complications from coronary artery disease 36. There are sex‐specific variations in NF‐κB activity, which may play a role in development of CED and atherosclerosis 37, 38…”

NF-κB and Enhancer-binding CREB Protein Scaffolded by CREB-binding Protein (CBP)/p300 Proteins Regulate CD59 Protein Expression to Protect Cells from Complement Attack

“…2B, inset). Meanwhile, it has been suggested that the deficient expression of mCRPs, especially CD59, is associated with autologous cell destruction by complement attack in autoimmune disorders, such as autoimmune hemolytic anemia, systemic lupus erythematosus, autoimmune thrombocytopenia, and aplastic anemia (4,5,30), possibly resulting from NF-B dysfunction due to genetic mutation (31). In addition, mouse CD59 genetic deficiency promotes atherogenesis in animal models (32); similarly, this study revealed the pathogenic roles of CD59 in atherosclerosis, a chronic inflammatory and immune vascular disease (33).…”

Down‐regulation of collagen and connective tissue growth factor expression with hepatocyte growth factor in lung fibroblasts from white scleroderma patients via two signaling pathways

“…Up-regulation of MMP-1 expression and activity by HGF in SSc lung fibroblasts appears to be regulated by MAPK-dependent and NF-B-independent pathways. NF-B is known to play an essential role in the regulation of a variety of genes involved in immune and inflammatory reactions leading to fibrogenic responses (34,35). HGF was reported to prevent vascular endothelial growth factor-induced and TNF␣-induced NF-B activation in endothelial cells (36,37).…”