Figure 7.
Bone marrow transfer from NLRP-3 and caspase-1–null mice to db/db mice is sufficient to downregulate the proinflammatory wound environment, upregulate a prohealing environment, and improve healing in diabetic mice. A and B: db/db Mice were subjected to lethal irradiation, and then bone marrow from wild-type (WT) or NLRP-3 (N3)–null mice was transferred 24 h later. Four weeks later, mice were subjected to excisional wounding, and wounds were harvested on day 10 postinjury, sectioned, and stained with hematoxylin-eosin. Note the increased re-epithelialization in db/db mice receiving NLRP-3 bone marrow. ep, epithelium; gt, granulation tissue. Arrows indicate ends of epithelial tongues, scale bar = 0.5 mm. C and D: Re-epithelialization and granulation tissue thickness measured in hematoxylin-eosin–stained cryosections of db/db mice receiving bone marrow from wild-type (WT-db) or NLRP-3–null (N3-db) or caspase-1–null (C1-db) mice. Trichrome staining measured as pixels stained blue for collagen (E) and CD31 staining measured as pixels stained for this endothelial cell marker (F). G–N: Levels of cytokines in wound homogenates measured using ELISA, including proinflammatory cytokines IL-1β, IL-18, TNF-α, and IL-6 and healing-associated cytokines IGF-1, TGF-β, IL-10, and VEGF. For all graphs, bars = mean ± SD, n = 6–8. Data compared between groups using ANOVA. *Mean value significantly different from that for mice receiving wild-type bone marrow; P < 0.05.