Role of interleukin-1β in hyperinflammation of chronic granulomatous disease

Objective To clarify the molecular mechanism underlying hyperinflammation in CGD(chronic granulomatous disease)induced by curdlan and demonstrates the potential mechanism involved in the link between NOX2 and hyperinflammation. Methods β-glucan is considered to be the main stimulus of the CGD inflammatory complication.In our study, mice model was established by 200 μg/50 μL/PBS 50 μL of curdlan (1, 3-β-glucan) injection into the ears of NOX2-/- mice.IL-1β protein in ears was detected using ELISA kit at day 2 and day 7.Caspase-1 was also detected by Western blot.In addition, bone marrow-derived macrophages (BMDM) isolated from these mice were treated with 10, 50, 100 and 200 μg/mL of curdlan.Supernatant of curdlan-treated macrophages was collected from day 1, 2 and 5 to detect level of IL-1β. Results NOX2 deficient mice (NOX2 KO) displayed hyperinflammation, increased ear thickness and elevated IL-1β level after curdlan injection (Day2: P=0.0189, Day 7: P=0.0450). The expression of active form of caspase-1 (caspase-1 p10) also increased (Day2: P=0.3980, Day 7: P=0.0001). In cell model, macrophages isolated from these mice were stimulated with 10, 50, 100, and 200 μg/mL of curdlan.IL-1β was up-regulated in BMDM (P=0.0011 at Day 5) and the level of IL-1 increased with a dose-dependent manner. Conclusions Curdlan led to high level of IL-1β production in macrophages through caspase-1 activation.IL-1β was involved in the hyperinflammation in chronic granulomatous disease induced by NOX2 deficiency. Key words: Chronic granulomatous disease; curdlan; NOX2; IL-1β