Aluminum-doped zinc oxide nanoparticles attenuate the TSLP levels via suppressing caspase-1 in activated mast cells

Zinc oxide nanoparticles (ZO-NPs) are used as antimicrobials, anti-inflammatories, and to treat cancer. However, although ZO-NPs have excellent efficiency and specificity, their cytotoxicity is higher than that of micron-sized zinc oxide. Doping ZO-NPs with aluminum can improve therapeutic efficacy, but the biological effects and mechanisms involved have not been elucidated. Here, we reported the efficacy of aluminum-doped ZO-NP (AZO) on thymic stromal lymphopoietin (TSLP) production and caspase-1 activation in human mast cell line, HMC-1 cells. AZO significantly reduced TSLP levels as well as interleukin (IL)-6, IL-8, and tumor necrosis factor (TNF)-α without inducing cytotoxicity. Furthermore, AZO more effectively reduced TSLP, IL-6, IL-8, and TNF-α levels than ZO-NP. The levels of inflammatory cytokine mRNA were also reduced by AZO treatment. AZO blocked production of IL-1β and activations of caspase-1 and nuclear factor-B by inhibiting IB kinase β and receptor interacting protein 2. In addition, AZO attenuated phosphorylation of mitogen-activated protein kinases, such as extracellular signal-regulated kinase, c-Jun N-terminal kinases, and p38. These findings provide evidence that AZO improves anti-inflammatory properties and offer a safe and effective potential treatment option.