High mobility group box protein-1 crossing cell borders may incite an inflammatory “tornado” in renal disease

Excerpt

High mobility group box 1 (HMGB-1) protein has been widely studied as a DNA-binding nuclear protein that regulates gene transcription, maintains nucleosome structure and modulates the activity of steroid hormone receptors [1]. Besides these classical functions as transcription factor, HMGB-1 may also be released by the cells into the extracellular milieu. This release process may be clearly distinguished from a passive process occurring with profound cell damage, e.g., necrosis or apoptosis, and has been elucidated as an active process in monocytes and macrophages after pro-inflammatory stimulation with LPS, IFN-γ, TNFα or IL-1β. “Outside” cells, HMGB-1 serves as an inflammatory mediator affecting synthesis of TNFα, monocyte chemotactic protein (MCP)-1 and expression of cell adhesion molecules ICAM-1 and VCAM-1 [2]. A recent publication by Oyama et al. [3] sheds light on the potent role of HMGB-1 in an experimental nephritis model caused by adenine excess. …