We have read with interest the article published by Singh et al. in the May 4, 2009 issue of The Journal of Immunology (1). NF-κB is an essential transcription factor for multiple genes related to the immune response and development (2, 3). Previous studies by our group and others also support the concept that NF-κB activation is essential for NOX2 activity, both in vitro and in vivo. Anrather et al., using a murine model, observed a lack of NADPH oxidase activity in leukocytes, fibroblasts, and neural cells after overexpression of IκBα and in a p65/RelA knockout (4). Our previous studies with dexamethasone, a steroid that inhibits NF-κB function, demonstrated inhibition of the phagocyte NADPH oxidase system at the transcriptional level (CYBB and NCF1 genes) in THP-1 myelomonocytic cells (5). Using U937 cells with a stable transfected repressor of NF-κB (IκBα-S32A/s36a) and EBV-transformed B cells from two patients with ectodermal dysplasia and immunodeficiency (EDA-ID), we found that proper binding of NF-κB is necessary for human CYBB and NCF1 gene expression and normal NADPH oxidase activity (6). Recently, our group observed that mononuclear cells from patients with EDA-ID produce less superoxide than normal control cells (Fig. 1⇓). Taken together, our current and previous observations (5, 6), and those of Singh et al. (1) all corroborate the essential role of NF-κB for proper function of the human phagocyte NADPH oxidase system.
- Copyright © 2009 by The American Association of Immunologists, Inc.