Fig. 4.

NLRP3 activation leads to severe liver inflammation. WT and Nlrp3 mutant mice were weaned after 21 days and placed on a normal chow for 4 weeks prior to induction of the knock-in mutation (in Nlrp3 mutants) by subcutaneous injections of tamoxifen. Analysis of liver histology revealed that Nlrp3 mutant mice fed with normal chow develop significantly more liver inflammation when compared to WT mice (a, b). Nlrp3 mutant mice also showed a significant increase in myeloid cells (assessed via immunohistochemistry for MPO) when compared to WT mice (a, d). In line with this finding, mRNA levels of Casp1, pro-IL-1β (c), CXCL2, and ICAM1 (e) were significantly elevated (p<0.05) in Nlrp3 mutant mice. Total macrophages (a, f) (assessed via immunohistochemistry and mRNA levels for F4/80) and Ly6c–positive macrophages (a, h) were increased in Nlrp3 mutant mice when compared to WT mice. Also, macrophages from Nlrp3 mutant mice showed aninflammatory M1 profile as evidenced by increased iNOS (g) and unchanged Arg1 (i) mRNA expression when compared to WT mice