Oxidative stress and NF-kappaB activation: correlation in patients following allogeneic bone marrow transplantation

• Published in: Antioxidants & redox signaling Vol. 2; no. 1; p. 93
• Main Authors: Blackwell, T S, Christman, J W, Hagan, T, Price, P, Edens, T, Morris, P E, Wolff, S N, Goodman, S A, Christman, B W
• Format: Journal Article
• Language: English
• Published: United States 2000
• Subjects: Adult; Antineoplastic Agents - adverse effects; Antineoplastic Agents - pharmacology; Bone Marrow Transplantation - adverse effects; Bronchoalveolar Lavage Fluid - chemistry; Cyclic AMP Response Element-Binding Protein - analysis; Dinoprost - analogs & derivatives; Dinoprost - urine; F2-Isoprostanes; Female; Gene Expression Regulation - physiology; Hematologic Neoplasms - metabolism; Hematologic Neoplasms - therapy; Humans; Inflammation - etiology; Inflammation - genetics; Lipid Peroxidation; Male; Middle Aged; NF-kappa B - metabolism; Oxidative Stress; Reactive Oxygen Species; Transcription, Genetic; Transplantation Conditioning - adverse effects; Transplantation, Homologous
• ISSN: 1523-0864

Although in vitro data has linked reactive oxygen species (ROS) to activation of nuclear factor kappaB (NF-kappaB), little data exist regarding this relationship in human disease. We hypothesized that bone marrow transplantation (BMT) would impart a degree of oxidative stress that might lead to in vivo activation of the redox-sensitive transcription factor NF-kappaB. Because NF-kappaB regulates transcription of many proinflammatory mediators, we reasoned that activation of NF-kappaB might contribute to the development of transplant-related complications. To evaluate NF-kappaB activation in humans, we measured NF-kappaB binding activity in nuclear extracts of bronchoalveolar lavage (BAL) cells obtained before and after allogeneic bone marrow transplantation (BMT) in 7 patients. Changes in BAL cell NF-kappaB binding activity were compared with changes in urinary F2-isoprostane concentration, an indicator of in vivo free radical-catalyzed lipid peroxidation. Although the extent of in vivo lipid peroxidation has substantial interindividual variability over time, we found a strong correlation between the pre/post-BMT ratio of urinary isoprostane concentrations and pre/post-BMT ratio of NF-kappaB binding activity in BAL cells, R = 0.96, p = 0.0005). This correlation is selective, because no relationship was found between the transcription factor CREB and urinary F2-isoprostane excretion. Although limited by the small number of patients studied, our data link oxidant stress to NF-kappaB activation in human alveolar macrophages following BMT. It is possible that such interactions may contribute to the clinical course after BMT by affecting transcription of proinflammatory genes.