Fig. 5: The in vivo stimulation of TRPML1 channel ameliorates clinical signs of DSS-induced colitis in mice by suppressing IL-1β production. | Nature Communications

Fig. 5: The in vivo stimulation of TRPML1 channel ameliorates clinical signs of DSS-induced colitis in mice by suppressing IL-1β production.

From: Lysosomes finely control macrophage inflammatory function via regulating the release of lysosomal Fe2+ through TRPML1 channel

Fig. 5

a Comparison of survival rate for C57BL/6 mice treated with 3% DSS or 3% DSS + ML-SA5 administration (0.1 mg/kg; IP injection) for 6 days (D). Mice were then monitored daily until day 12. n = 6. b Percentage of weight changes of mice treated with vehicle (n = 45), 3% DSS administration (n = 28), 3% DSS + ML-SA5 (0.1 mg/kg) administration (n = 5), or 3% DSS + ML-SA5 (0.1 mg/kg) + ML-SI3 (0.5 mg/kg) administration (n = 10) for 6 days. Initial weight of each mouse was defined as 100%. c A time course of disease activity index (DAI) for the mice shown in (b) was monitored daily until day 7. d Representative images and length measurement of colons from mice treated with vehicle, 3% DSS administration, 3% DSS + ML-SA5 (0.1 mg/kg) administration, 3% DSS + ML-SA5 (0.1 mg/kg) + ML-SI3 (0.5 mg/kg) administration, or ML-SA5 (0.1 mg/kg) alone for 6 days. n = 6–35. e Representative H&E staining of colons from mice treated with vehicle, 3% DSS administration, 3% DSS + ML-SA5 (0.1 mg/kg) administration (n = 5), or 3% DSS + ML-SA5 (0.1 mg/kg) + ML-SI3 (0.5 mg/kg) administration for 6 days. Scale bar = 50 μm. Histological analysis of colon tissue from mice under indicated administration at day 7. n = 15–18. f Representative IL-1β staining of colonic tissues collected from mice treated with vehicle, 3% DSS administration, 3% DSS + ML-SA5 (0.1 mg/kg) administration, or ML-SA5 (0.1 mg/kg) administration alone for 6 days. Relative IL-1β fluorescence intensity was normalized to the vehicle group. Scale bar = 50 μm. n = 5–8. g IL-1β levels in serum collected from mice treated with vehicle, 3% DSS administration, 3% DSS + ML-SA5 (0.1 mg/kg) administration, or 3% DSS + ML-SA5 (0.1 mg/kg) + ML-SI3 (0.5 mg/kg) administration for 6 days, as assessed by ELISA assay. The line inside the box denotes the median value, while the top and bottom of the box contain the 25th to 75th percentiles of the dataset. The whiskers indicate the minimum and maximum values. n = 5. Means ± SEMs were shown in a–f. Significant differences were evaluated using one-way ANOVA followed by Tukey’s test.

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