Transcriptional Regulation of SerpinB2 (Plasminogen Activator Inhibitor type 2/PAI‐2) and its Role in Macrophage Survival

Macrophages are the key mediators in the innate immune response – as they are responsible for its initiation, modulation, and eventual termination. Macrophages also play a role in establishing immunological memory through the adaptive immune response, since they are able to serve as professional antigen presenting cells. Once activated by a pro‐inflammatory stimulus, such as bacterial lipopolysaccharide (LPS), macrophages produce a wide array of cytokines and chemokines, and undergo dramatic changes in signaling, transcriptional activity, and protein expression, often through Toll‐like receptor (TLR)‐mediated pathways. The serine protease inhibitor, SerpinB2 (also known as Plasminogen activator inhibitor type 2), has been implicated in mediating a cytoprotective effect on macrophages. Here we investigate the mechanisms underlying LPS regulation of SerpinB2. Our results indicate that the LPS‐mediated response of the murine SerpinB2 proximal promoter is dependent on at least four transcription factors, C/EBPβ, AP‐1, CREB, and NF‐κB. Transcriptional activation of SerpinB2 takes place within one hour following LPS exposure, yet apparent protein expression is not seen until at least eight hours following LPS exposure. These data provide evidence of a gene‐regulatory network that works to achieve maximal activation of SerpinB2 in macrophages.