Fig. 2: IDO-Gal3 prevents and inhibits periodontal disease progression.
From: Suppression of local inflammation via galectin-anchored indoleamine 2,3-dioxygenase
a,b, Efficacy was investigated using a polymicrobial mouse model of periodontal disease and either prophylactic (a) or therapeutic (b) administration. c,d, Anchored-fusion reporter enzyme NanoLuc-Gal3 (NL-Gal3) injected submandibularly was retained locally for 120 h, by in vivo imaging (c), in contrast to unanchored NanoLuc which diffused away from the injection site (d, dashed line represents baseline). e, Infection state did not alter submandibular retention time of NL-Gal3; dotted line represents baseline. f–h, Representative images of micro-CT analysis (f) quantifying trabecular bone volume (g) and vertical bone loss (h), by measuring the cementoenamel junction. In f: scale bar, 1.5 mm; the yellow box represents the standardized ROI of 5.5 mm3, based on 1.5 × 4.0 × 1.0 mm (vertical or cervico-apical × horizontal or mesio-distal × lateral or buccal-palatal); the orange lines indicate the measured distances between the CEJ and the alveolar bone crest (n = 12). Submandibular injection of IDO-Gal3 blocked mandibular bone loss in prophylactic (IDO-Gal3-P) administration and halted mandibular bone loss in therapeutic (IDO-Gal3-T) administration. i–k, IDO-Gal3 reduced gingival inflammatory protein levels of IL-6 (i), IL-1β (j) and MCP1 (k), with a more pronounced effect from therapeutic administration (IDO-Gal3-T). l, IDO-Gal3 induced the expression of IL-10 protein, restoring levels closer to that of the uninfected control (Uninfect). IDO-Gal3 administered to uninfected mice (IDO-Gal3-U) had negligible effect on mandibular bone and production of inflammatory cytokines while increasing levels of IL-10 and to a smaller extent, MCP1. Data shown as mean ± s.e.m. (d and e) and mean ± s.d. (g–l). Statistical analysis: (e) Student’s t-test; n = 5; (g–l) one-way ANOVA with Tukey’s post-hoc test, n = 5. For (g), P < 0.0001, F = 20.41. For h, P < 0.0001, F = 75.53. For i, P < 0.0001, F = 73.69. For j, P < 0.0001, F = 44.24. For k, P < 0.0001, F = 66.63. For l, P < 0.0001, F = 122.8. For g–l, unless otherwise specified, pairwise P values from Tukey’s post-hoc analysis are reported as ‘X, Y’, where X represents comparison to ‘Infect’ and Y represents comparison to ‘Uninfect’; ****P < 0.0001.
