Figure 5.
Titanium triggers inflammasome activation. Titanium particle internalization triggers the release of Cathepsin B from lysosomes, which together activate Nalp3. Activated Nalp3 recruits ASC through PYD domain interactions. This complex triggers cleavage and recruitment of activated Caspase-1 through CARD domain interactions. This inflammasome complex then cleaves pro-IL-1β into its active, secreted form IL-1β, which can trigger downstream IL-1 associated signaling, including neutrophil recruitment, through activation of the IL-1R. This acute inflammatory response can be inhibited with IL-1Ra treatment.