[WS8-3] TRIF- HIF-1α signaling under hypoxia drives enhancement of inflammasome activation by P. gingivalis
The microenvironment of human tissue associated with microbial infection (e.g. periodontal pocket, tubercle) is exposed under hypoxia, and which contribute to regulation of immune response. In the absence of oxygen, hypoxia-inducible factor-1 alpha (HIF-1α) binds to hypoxia-response elements (HREs), and thereby activating the expression of numerous hypoxia-response genes. Some reports suggested HREs has relation with progression of infectious diseases, but the mechanisms are elusive. Periodontal pockets in patients are always exposed under hypoxia, and colonized by periodontitis associated bacteria containing Porphyromonas gingivalis (Pg). Considering from majority of bacteria from periodontal pockets are anaerobic bacteria, hypoxia is important factor to form pathogenesis in periodontitis. In this study, we investigated the inflammasome activation that regulates caspase-1 activation and IL-1βmaturation by Pg infection under hypoxia. We demonstrated that hypoxia provokes the enhancement of inflammasome activation by Pg in TIR-domain-containing adapter-inducing interferon (TRIF) and HIF-1α dependent manner. We also observed TRIF drives stability of HIF-1α in cytosol under hypoxia. These results elucidate new insight of the molecular bases for the mechanisms underlying hypoxia contributes to progression of pathogenesis in periodontitis by Pg-triggered inflammasome activation.