ovalbumin and shikonin

Immunoadjuvants, as an indispensable component of tumor vaccines, can observably enhance the magnitude, breadth, and durability of antitumor immunity. However, current immunoadjuvants suffer from different issues such as weak immunogenicity, inadequate cellular internalization, poor circulation time, and mono-functional bioactivity.

Topics: Adjuvants, Immunologic; Antigens; Cancer Vaccines; Cell Line, Tumor; Ferric Compounds; Humans; Immunogenic Cell Death; Immunotherapy; Nanomedicine; Neoplasms; Ovalbumin; Tissue Distribution; Tumor Microenvironment; Vaccination

Allergic rhinitis (AR) is a disease in the nasal mucosa related with Th2 lymphocyte inflammatory action. Dendritic cells (DCs) have been proved that they played a significant role in the development and maintenance of AR. However, there is still a lack of specific therapies for DCs in clinical practice. Shikonin (SHI) is a natural naphthoquinone compound isolated from the Chinese herb Radix Arnebiae. It is reported that SHI can interference the phenotype and function of dendritic cells, so we speculate that SHI may be an effective drug for the treatment of AR. However, the clinical usage of SHI has been limited by the bioactive properties of poor solubility, short retention time and low bioavailability. Therefore, in order to better exert the anti-inflammatory effect of SHI, an efficient SHI delivery system is urgently needed.. We prepared and characterized SHI-PM and NGR-SHI-PM with the thin-film hydration method. We used retrodialysis method to explore the release behavior. We took immunofluorescence to investigate the expression of CD13 in vitro. Then we tested BM-DCs mature cell detection by flow cytometry. An allergic rhinosinusitis murine model, hematoxylin and eosin stain and flow cytometry were established to test the efficiency of anti-inflammation in vivo. At last, western blot analysis and plasmid construction and transfection assay were taken to reveal the molecular mechanisms.. In the present study, we revealed that NGR-modifified could strengthen the intracellular uptake of PM (p < 0.001) and CD13 was high expressed on mature BM-DCs (p < 0.001). NGR-modified could enhance the inhibition of SHI in vitro (p < 0.05). NGR-modifified could increase the distribution of PM in vivo by DiI fluorescently (p < 0.01). NGR-modified could enhance SHI anti-allergic activity in OVA-sensitized mice and enhance the inhibition of SHI on DC maturation in lymph node (p < 0.001). Our findings also suggest that SHI may have the inhibitory effect on AR through NF-κB pathway by targeting PARP.. In summary, we have shown that NGR-PM-SHI could be a novel strategy for targeted treating allergic rhinitis through the NF-κB pathway by targeting PARP.

Topics: Animals; Dendritic Cells; Disease Models, Animal; Mice; Mice, Inbred BALB C; Micelles; Naphthoquinones; Nasal Mucosa; NF-kappa B; Ovalbumin; Poly(ADP-ribose) Polymerase Inhibitors; Polyesters; Polyethylene Glycols; Rhinitis, Allergic

Shikonin exhibits a wide range of anti-inflammatory actions. Here, we assessed its effects on maturation of murine bone marrow-derived dendritic cells (BM-DCs) and on allergic reactions in a murine model of asthma.. Cultured murine BM-DCs were used to investigate the effects of shikonin on expression of cell surface markers and their stimulation of T-cell proliferation and cytokine production. The therapeutic potential of shikonin was evaluated in a model of allergic airway disease.. Shikonin dose-dependently inhibited expression of major histocompatibility complex class II, CD80, CD86, CCR7 and OX40L on BM-DCs, induced by a mixture of ovalbumin (OVA; 100µg·mL(-1) ) and thymic stromal lymphopoietin (TSLP; 20ng·mL(-1) ). Shikonin-treated BM-DCs were poor stimulators of CD4(+) T lymphocyte and induced lower levels of interleukin (IL)-4, IL-5, IL-13 and tumour necrosis factor (TNF)-α release by responding T-cells. After intratracheal instillation of shikonin in OVA-immunized mice, OVA challenge induced lower IL-4, IL-5, IL-13, TNF-α and eotaxin release in bronchial alveolar lavage fluid, lower IL-4 and IL-5 production in lung cells and mediastinal lymph node cells and attenuated OVA-induced lung eosinophilia and airway hyperresponsiveness.. Shikonin effectively suppressed OVA + TSLP-induced BM-DC maturation in vitro and inhibited allergic inflammation and airway hyperresponsiveness in a murine model of asthma, showing good potential as a treatment for allergic asthma. Also, our model provides a novel platform for screening drugs for allergic diseases.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Asthma; Bone Marrow Cells; Bronchoalveolar Lavage Fluid; Cytokines; Dendritic Cells; Drugs, Chinese Herbal; Female; Inflammation; Interleukin-13; Interleukin-4; Interleukin-5; Lung; Mice; Mice, Inbred BALB C; Naphthoquinones; Ovalbumin; Thymic Stromal Lymphopoietin; Tumor Necrosis Factor-alpha