Hepatocellular carcinoma (HCC) is a typical hypervascular tumor. Our previous studies have demonstrated that hepatitis B virus X protein (HBx) was able to inhibit the growth of HCC cells via inducing apoptosis and inhibiting tumor angiogenesis. Interleukin-12 (IL-12) is a disulfide-linked heterodimeric cytokine with potent immunostimulatory activity and anti-angiogenic properties. In this study, to further investigate the regulatory effect of IL-12 on HBx-mediated intervention of hepatoma microenvironment especially on intervention of neovessels and immune microenvironment, we constructed the recombinant adenovirus expressing HBx and mouse IL-12 named Ad-HBx-mIL-12. HBx-mIL-12 could effectively suppress tumor growth and induce apoptosis in vivo. Moreover, treatment with Ad-HBx-mIL-12 not only induced a massive accumulation of immune cells (CD8 + T leukocytes, macrophages and dendritic cells) in tumors in situ, also apparently reduced the number of angiogenic blood vessels within tumor tissues. These results suggest that HBx-mIL-12 can not only induce cell cycle arrest and apoptosis in HCC cells, but also effectively shift the tumor microenvironment from pro-oncogenic to antitumor through recruitment of immune cells and inhibiting stromal cell growth, such as vascular endothelial cells.
Asthma is an atopic disorder with increasing frequency and severity in developed nations. Interleukin-13 (IL-13) is one of the most critical mediators of asthma pathology. In the present study, we developed a vaccine comprised of a keyhole limpet hemocyanin-mIL-13 heterocomplex immunogen to persistently neutralize excessive endogenous IL-13. Our results showed that the IL-13 peptide kinoid vaccine could induce sustained and high titer of IL-13-specific IgG when using aluminum hydroxide as an adjuvant, and could suppress the accumulation of eosinophils as well as IL-13 levels in bronchoalveolar lavage fluid (BALF). In addition, total IgE and ovalbumin (OVA)-specific IgE in serum were significantly inhibited. This study also showed that vaccination could prevent airway inflammation and epithelial cell proliferation with goblet cell hyperplasia in a mouse model of acute asthma. In summary, our findings suggest that the IL-13 peptide kinoid can serve as an innovative and effective vaccine against asthma.
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