The biological roles of the dual oxidases, DUOX1 and DUOX2, are dependent upon the tissue in which they are expressed. However, the mechanisms that control DUOX expression in these tissues are largely unexplored. Given the known role of DUOX for host defense in the gut and respiratory tract, we characterized potential mechanisms that control DUOX2 expression in response to interferon gamma (IFN gamma) in respiratory tract epithelium. We discovered that IFN gamma-mediated DUOX2 expression was regulated by a STAT-independent, JAK-independent pathway. These data provide insights into a novel IFN gamma signaling pathway with potential importance for regulation of host defense responses. (C) 2010 Elsevier Inc. All rights reserved.