Figure 9.

Schematic diagram showing the mechanism of NLRP3 inflammasome activation by LPA₁. In injured brains after tMCAO challenge, NLRP3 is upregulated in the penumbra and ischemic core regions, particularly in cells expressing Iba1 (a marker of macrophages). NLRP3 inflammasome activation including ASC speck formation, caspase-1 activation, and IL-1β maturation occurs in injured brains. LPA₁ contributes to NLRP3 upregulation (Signal 1) and NLRP3 inflammasome activation (Signal 2) in injured brains. In cultured macrophages, LPA₁ also regulates NLRP3 upregulation and NLRP3 inflammasome activation (caspase-1 activation, IL-1β maturation, and IL-1β secretion) in LPS-primed macrophages, followed by LPA exposure. As underlying mechanisms, LPA₁ regulates translocation of NF-κB into the nucleus and activation of p38 and ERK1/2 in these stimulated macrophages. It has been reported that LPA₁ can regulate such underlying mechanisms in injured brains after ischemic challenge [4].