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. Author manuscript; available in PMC: 2015 Jun 11.
Published in final edited form as: Nature. 2014 Sep 28;516(7530):246–249. doi: 10.1038/nature13788

Figure 4. Compensatory processing of IL-1β by caspase-1 and caspase-8 in neutrophils drives inflammatory bone disease.

Figure 4

a, Incidence of osteomyelitic disease in Pstpip2cmo, Pstpip2cmoxCasp1−/−, Pstpip2cmoxRip3−/−xCasp8−/−, Pstpip2cmoxCasp1−/−xRip3−/−xCasp8−/− (TKO) and Pstpip2cmoxIl1β−/− mice over time. b, Representative H&E staining of hind paw sections. c, Western blot analysis of IL-1β regulation in the footpads of 10-12 week old Pstpip2cmo, Pstpip2cmoxCasp1−/−, Pstpip2cmoxRip3−/−xCasp8−/−, Pstpip2cmoxCasp1−/−xRip3−/−xCasp8−/− (TKO) and Pstpip2cmoxIl1β−/− mice. d-f, WT and Pstpip2cmo bone marrow-derived macrophages (d) or neutrophils (e-f) were left untreated (UT) or were first primed with LPS for 3 hrs followed by stimulation with ATP (30 mins) or silica (12 hrs). d-e, Secretion of IL-1β was measured by ELISA. Bar graphs depict mean ± s.e.m. One out of three biological replicates, with two-three technical replicates each. f, Western blot analysis of IL-1β in WT, Pstpip2cmo, Pstpip2cmoxCasp1−/− and Pstpip2cmoxCasp1−/−xRip3−/−xCasp8−/− (TKO) neutrophils. g-i, WT and Pstpip2cmo mice received either PBS or anti-Ly6G antibody every 4-5 days starting at 6 weeks of age. g, Incidence of inflammatory bone disease. h-i, Representative footpad images (h) and tail H&E micrographs (i).