Tissue plasminogen activator and inflammation: from phenotype to signaling mechanisms

Abstract

In disease conditions, inflammatory cells, such as neutrophils, T cells, and monocytes/macrophages, are recruited in response to injury cues and express panoply of proinflammatory genes through a combination of transcription factors. Tissue plasminogen activator (tPA), a member of the serine protease family, has been shown to act as cytokine to activate profound receptor-mediated signaling events. In this review, we will discuss the role of tPA in inflammation in various models, and illuminate its signaling mechanisms underlying its modulation of inflammation.

Keywords: Tissue plasminogen activator; inflammation; phenotype; signaling mechanisms; tPA.

Figure 1

Mechanisms of tPA in modulating inflammation. A: tPA binds to LRP-1 and induces activation of NF-κB. B: tPA promotes the aggregation of annexin A2 and integrin CD11b, leading to activation of ILK, phosphorylation and degradation of IκB, and eventually activation of NF-κB. C: tPA forms complex with LRP-1, PAI-1, and Mac-1, which results in the increased macrophage migration.