Mycobacterial Infection induces the secretion of High mobility group box 1 (HMGB1) protein (43.20)

Abstract High mobility group box protein 1 (HMGB1) is a nonhistone nuclear protein that acts as a pro-inflammatory cytokine and is released by monocytes and macrophages. Necrotic cells also secrete HMGB1 at the site of tissue damage that induces a variety of cellularresponses, including expression of proinflammatory mediatorssuch as TNF- , IL-1, and NO. This study investigated the secretion of HMGB1 during mycobacterial infection of macrophages in vitro and in the lungs of infected guinea pigs. We observed that infection with mycobacterium effectively induced HMGB1 release in both macrophage and monocytic cell cultures. Culture filtrate proteins from Mycobacterium tuberculosis (including Ag85A, Ag85B, ESAT-6 and CFP-10) induced maximum release of HMGB1 among different cellular components of mycobacterium. We demonstrated that HMGB1 is released by lung cells during infection of M. tuberculosis in guinea pig and increased HMGB1 secretion in lungs of guinea pigs was delayed by vaccination with BCG. The secretion of cytokines like TNF-α and IL-1β were significantly increased when J774A.1 cell cultures were incubated with HMGB1 during infection with M. bovis BCG. We conclude that HMGB1 is secreted by macrophages during tuberculosis and it may act as a signal of tissue or cellular injury and may act as a precursor to enhance the immune response. Funding for this research was provided by NIH AI40091 (A.A.I.).