The Biologic Role for Nuclear Factor-KappaB in Disease and its Potential Involvement in Mucosal Injury Associated with Anti-neoplastic Therapy

Abstract

Oral mucosal barrier injury (mucositis) is a frequent, painful, serious, dose-limiting toxicity associated with many anti-neoplastic drugs and radiation to the head and neck. Results of recent studies suggest that mucositis is the result of a complex series of interactive biological events that take place in the submucosa and epithelium. The nuclear transcription factor NF-κB has been implicated in the control of a broad range of biological responses, the activation of a large number of specific cellular genes, and the determination of the fate of cells exposed to ionizing radiation and anti-neoplastic drugs. Of particular importance to mucositis is the fact that NF-κB regulates key elements in the apparent sequence that leads to normal tissue toxicity. Not the least of these is the effect that NF-κB activation has on apoptosis. In particular, a paradox exists between the potential pro-apoptotic effect NF-κB exerts on normal cells, and the anti-apoptotic and cytoprotective effect it causes in tumor cells. This paper provides a review of the structure and function of NF-κB and speculates how its apparent enigmatic effect on normal and tumor cells may occur.