TNF and ischemia: Leukocytes (Neutrophils) (not primary source). Mechanisms for MMP-9 activation following ischemia include: (1) ROS (2) TNF, IL-1β, and other cytokines that activate MMP-3 which converts proMMP-9 to active MMP-9 (3) actions of high mobility group box protein1 (HMGB1) on TLR4 receptors that then induce MMP-9 or (4) NF-κB induction of MMP-9