At the time we initiated our studies on the molecular characterization of cytokines, namely interferons and interleukins, the conventional wisdom was that cytokines were soluble factors secreted upon activation of cells by various stimuli, such as upon virus infection. It was in this context that we discovered the type I IFN gene family and, subsequently, a family of transcription factors, termed interferon regulatory factors (IRFs), as crucial regulators of type I IFN and other cytokine systems. The IRF family is now recognized for its broad role in immunity and oncogenesis.
Subsequently we encountered another class of cytokine-like molecules called damage-associated molecular patterns (DAMPs) that function intracellularly and extracellularly as soluble factors to exert seemingly unrelated biological activities. High-mobility group box protein1 (HMGB1) is a typical DAMP molecule that has been extensively studied for its protective and pathogenic functions.
In this lecture, I will present data on how HMGB1, which we originally identified as a general sensor of immunogenic nucleic acids, is released from the nucleus and how it functions to regulate inflammation and cancer metastasis. Our recent data indicate that HMGB1 exerts its function via a mechanism that is distinct from what has been widely appreciated heretofore. If time permits, I will also present our results on other DAMPs that may also participate to the regulation of inflammation and cancer.