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-1ß and activations of caspase-1 and nuclear factor-κB by inhibiting IκB kinase ß 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.

The therapeutic efficacy of α-pinene in an experimental mouse model of allergic rhinitis.

In the present study, the therapeutic effect and underlying mechanism of α-pinene (α-PN) in the ovalbumin (OVA)-sensitized allergic rhinitis (AR) model were investigated. Our results showed that pretreatment with α-PN caused a decrease in clinical symptoms, including a decrease in the number of nasal, eye, and ear rubs, and spleen weight in the OVA-sensitized mice. The level of interleukin (IL)-4 was decreased on the spleen tissue of α-PN treated mice. Pretreatment with α-PN significantly decreased levels of nasal immunoglobulin E. Protein levels of tumor necrosis factor-α, intercellular adhesion molecule-1, and macrophage inflammatory protein-2 were decreased by the administration of α-PN in the nasal mucosa of the OVA-sensitized mice. The increased numbers of eosinophils and mast cells infiltrating the nasal mucosal tissue of mice with AR were decreased following oral administration of α-PN. Post-treatment with α-PN 1h after OVA challenge also resulted in a significant reduction of clinical symptoms and IgE levels. In addition, the expression and phosphorylation of receptor-interacting protein 2 (RIP2) and IκB kinase (IKK)-ß and activation of nuclear factor-κB (NF-κB), and caspase-1 were all increased in the activated human mast cell line, HMC-1 cells, however, increased activations of RIP2, IKK-ß, NF-κB, and caspase-1 were inhibited by treatment with α-PN. Taken together, we suggest that α-PN is a promising anti-allergic agent and may be useful in the clinical management of AR.

Zinc oxide nanoparticles, a novel candidate for the treatment of allergic inflammatory diseases.

Zinc (Zn) is an essential trace metal for eukaryotes. The roles of Zn in the numerous physiological functions have been elucidated. Bamboo salt contains Zn that was shown to have anti-inflammatory effect and other health benefits. Nanoparticles of various types have found application in the biology, medicine, and physics. Here we synthesized tetrapod-like, zinc oxide nanoparticles (ZO-NP; diameter 200 nm, source of Zn) using a radio frequency thermal plasma system and investigated its effects on mast cell-mediated allergic inflammatory reactions. ZO-NP was found to inhibit the productions and mRNA expressions of inflammatory cytokines such as interleukin (IL)-1ß, IL-6, and tumor necrosis factor-α on the phorbol 12-myristate 13-acetate plus A23187 (PMACI)-stimulated human mast cell line, HMC-1 cells. In these stimulated cells, caspase-1 and nuclear factor-κB activations were abolished by ZO-NP, and the expressions of receptor interacting protein2 (RIP2) and IκB kinaseß (IKKß) induced by PAMCI were reduced. On the other hand, ZO-NP alone increased the expressions of RIP2 and IKKß in normal condition. ZO-NP inhibited the phosphorylation of extracellular signal-regulated protein kinase in the PMACI-stimulated HMC-1 cells. Furthermore, ZO-NP significantly inhibited passive cutaneous anaphylaxis activated by anti-dinitrophenyl IgE. These findings indicate that ZO-NP effectively ameliorates mast cell-mediated allergic inflammatory reaction, and suggest that ZO-NP be considered a potential therapeutic for the treatment of mast cell-mediated allergic diseases.