TNF-α signaling and cathepsin B

Tumor necrosis factor-α (TNF-α) has many physiological roles in homeostasis, including the regulation of cell survival and apoptosis. In addition, TNF-α plays a central role in the inflammation and innate immunity following its overproduction. Macrophages and microglia are widely accepted as major TNF-α producers as well as responders in systemic inflammation and the subsequent neuroinflammation, respectively. Because TNF-α plays a crucial role in the inflammatory responses and innate immunity, it is an attractive therapeutic target for the treatment of patients with rheumatoid arthritis, atherosclerosis and Alzheimer's disease. There is increasing evidence that cathepsin B (CatB), a typical lysosomal cysteine protease, is involved in TNF-α signaling and innate immunity. We herein describe the roles of CatB in TNF-α signaling-mediated apoptosis, inflammation and innate immunity. In addition, we discuss a possible therapeutic usefulness of CatB inhibitors on the treatment for inflammatory diseases.