LUTEOLIN–GADOLINIUM COMPLEX ATTENUATES INFLAMMATORY RESPONSES AND MODULATES STAT3–NLRP3 SIGNALING IN COMPOUND 48/80-STIMULATED HMC-1 CELLS

Mast cell activation and inflammatory mediator release are central to the pathogenesis of urticaria. Luteolin has anti-inflammatory and anti-allergic properties; however, the effects and underlying mechanisms of the luteolin–gadolinium rare-earth complex (LutGdRCS) in mast cells remain unclear. This study investigated the effects of LutGdRCS on inflammatory responses and STAT3–NLRP3 signaling in Compound 48/80-stimulated HMC-1 cells. Cell viability and membrane integrity were assessed using Cell Counting Kit-8 and lactate dehydrogenase (LDH) release assays, respectively. Histamine, interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α concentrations in culture supernatants were quantified by enzyme-linked immunosorbent assay, and proteins associated with STAT3–NLRP3 signaling were assessed by Western blotting. At the concentrations used for subsequent experiments, Compound 48/80 (10 μg/mL), luteolin (2.5 μg/mL), and LutGdRCS (10 μg/mL) did not significantly reduce cell viability or increase LDH release. Compound 48/80 significantly increased histamine, IL-1β, IL-6, and TNF-α concentrations in culture supernatants, whereas luteolin and LutGdRCS significantly attenuated these increases (P < 0.05). Western blotting further showed that LutGdRCS reduced p-STAT3, NLRP3, caspase-1 p20, and IL-1β p17 protein levels in stimulated cells. These findings indicate that LutGdRCS attenuates inflammatory mediator responses in HMC-1 cells and that these effects are associated with reduced p-STAT3 levels and NLRP3 inflammasome signaling, supporting further investigation of LutGdRCS in experimental mast cell-mediated inflammation.