A Novel Application of Ti-Substituted Polyoxometalates: Anti-Inflammatory Activity in OVA-Induced Asthma Murine Model

Abstract

Objective. Asthma is a chronic inflammatory disorder. Despite extensive researches into the treatment and management of it, current treatments and management strategies are still limited. The search for a novel approach to its treatments is urgently needed. Researches on the potential medical use of polyoxometalates (POMs) have already shown it has antiviral and antitumor bioactivities. But the effects of POM in immune systems are still largely unknown. Methods. In order to investigate the role of POM in the asthmatic disease, we used OVA-induced asthma murine model and observed the pathological changes between mice that received three different Ti-substituted POMs (0.3 μg per mouse per dose) when challenged with OVA. We also measured the type 2 cytokine expressions to reveal the potential mechanism. Results and Conclusions. Our results showed that two Ti-substituted POMs, K5H2[FeW11TiO40]·17H2O and K5H[H2ZnW11TiO40]·35H2O, could reduce OVA-induced lung inflammation, serum IgE level (around 2000 ng/mL to less than 1000 ng/mL), leukocytes infiltration in the lung, and cytokines levels (including IL-4, IL-5, IL-13, and TNF-α) but Ti-centered POM K4[TiW12O40]·10H2O did not. Thus, Ti-substituted POMs may have pharmaceutical values especially in treatments for asthmatic diseases.

Figure 1

Polyoxometalates FeWTi and ZnWTi reduce OVA-induced lung inflammation. (a) Lung H&E staining; (b) lung pathology score; (c) serum IgE level measured by ELISA; bars = SEM; n = 7 mice/group/experiment; scale bar = 100 μm; ^∗ p < 0.05 compared to mouse treated with TiW. Data are representative of 3 experiments.

Figure 2

Polyoxometalates FeWTi and ZnWTi reduce inflammatory cells infiltration in the airway. Cells in the BALF were stained and counted; numbers of (a) total cells, (b) macrophages, (c) neutrophils, (d) lymphocytes, and (e) eosinophils; bars = SEM; n = 7 mice/group/experiment; ^∗ p < 0.05 compared to mouse treated with TiW. Data are representative of 3 experiments.

Figure 3

Polyoxometalates FeWTi and ZnWTi reduce inflammatory cytokines profile in OVA-induced asthma. Cytokines in the BALF were measured by ELISA; the concentration of (a) IL-4, (b) IL-5, (c) IFN-γ, (d) IL-13, and (e) TNF-α; bars = SEM; n = 7 mice/group/experiment; ^∗ p < 0.05 compared to mouse treated with TiW. Data are representative of 3 experiments.

Figure 4

Polyoxometalates FeWTi and ZnWTi reduce mRNA expression of inflammatory cytokines in OVA-induced asthma. The mRNA expressions of cytokines of lung tissues were measured by q-PCR; the expression of (a) Il4, (b) Il5, (c) Ifng, (d) Il13, and (e) Tnf; bars = SEM; n = 7 mice/group/experiment; ^∗ p < 0.05 compared to mouse treated with TiW. Data are representative of 3 experiments.

Figure 5

Polyoxometalates FeWTi and ZnWTi suppress the degranulation of mast cells. Mast cells were stimulated by ionomycin and PMA with or without different doses of TiW, FeWTi, or ZnWTi for 1 hour; the concentrations of histamine in supernatant were measured by ELISA. The inhibition rate was calculated by comparing the histamine expression of mast cells treated with different chemicals to mast cells treated with completed media. ^∗ p < 0.05 compared to mouse treated with TiW. Data are representative of 3 experiments.

Figure 6

Keggin anion structure. (a) TiW₁₂O₄₀ ⁴⁻ and (b) Fe(Zn)W₁₁TiO₄₀ ^5−/6−.