[Effects of sIL-13Rα2 on the nasal mucosa goblet cell apoptosis of allergic rhinitis of rats].

Objective: To investigate the effects of sIL-13Rα2 on the apoptosis of goblet cell in nasal mucosa of allergic rhinitis rats. Methods: Forty healthy male Wistar rats were randomly divided into 4 groups (10 rats per group): control group (group A), AR group (group B), sIL-13Rα2 group (group C) and triamcinolone acetonide group (group D). Ovalbumin (OVA) and aluminum hydroxide were used to establish the AR rat model. After the establishment of AR rat models, 50 µl PBS, 100 µg/50 µl IL-13Rα2 and 3.5 µg/50 µl triamcinolone acetonide were respectively dropped into each nasal cavity of every rat two times a week from 4 to 10 week in group B, group C and group D. Group A was operated with saline instead of OVA. The nasal mucosa tissues were collected at 24 h after the final administration. AB-PAS staining method was used to detect the quantity and secretion of goblet cells in the nasal mucosa tissue of all groups. Immunohistochemistry method was used to detect the expression of Bax proteins.Apoptosis was detected by TUNEL method.ANOVA analysis was used to compare multiple groups, and LSD-t test was used to compare the two groups.Pearson correlation analysis was used to analyze the correlation between the Bax positive cell rate of goblet cells and the rate of apoptotic cells. The difference was statistically significant with P<0.05. Results: Compared with group A, there were more goblet cells and hypersecretion of mucus in the nasal mucosa tissue of rats in group B while fewer in group C. The goblet cells in group C and group D were significantly fewer than that in group B (0.639 00±0.831 vs 0.956 7±0.980, 0.661 90±0.657 vs 0.956 7±0.980, t value was 2.748, 2.767, respectively, all P<0.05). The immunohistochemistry results showed that the positive expression rates of Bax protein in goblet cells of group C and group D were significantly higher than that in group B (0.880 2±0.125 vs 0.568 7±0.953, 0.938 4±0.200 vs 0.568 7±0.953, t value was -2.292, -2.685, respectively, all P<0.05). The apoptosis rates of goblet cell in nasal mucosa of group C and group D were also significantly higher than that in group B (0.516 0±0.079 vs 0.274 0±0.056, 0.535 4±0.829 vs 0.274 0±0.056, t value was -17.671, -2.225, respectively, all P<0.05). The expression of Bax protein and apoptosis of goblet cells were positively correlated (r=0.859, P<0.01). Conclusion: sIL-13Rα2 can induce apoptosis of the goblet cells in nasal mucosa of allergic rhinitis rats, by inhibiting IL-13 and up regulating Bax.

PEGylated Polyamidoamine dendrimer conjugated with tumor homing peptide as a potential targeted delivery system for glioma.

Glioblastoma multiforme (GBM) is the most common and aggressive primary central nervous system (CNS) tumor with a short survival time. The failure of chemotherapy is ascribed to the low transport of chemotherapeutics across the Blood Brain Tumor Barrier (BBTB) and poor penetration into tumor tissue. In order to overcome the two barriers, small nanoparticles with active targeted capability are urgently needed for GBM drug delivery. In this study, we proposed PEGylated Polyamidoamine (PAMAM) dendrimer nanoparticles conjugated with glioma homing peptides (Pep-1) as potential glioma targeting delivery system (Pep-PEG-PAMAM), where PEGylated PAMAM dendrimer nanoparticle was utilized as carrier due to its small size and perfect penetration into tumor and Pep-1 was used to overcome BBTB via interleukin 13 receptor α2 (IL-13Rα2) mediated endocytosis. The preliminary availability and safety of Pep-PEG-PAMAM as a nanocarrier for glioma was evaluated. In vitro results indicated that a significantly higher amount of Pep-PEG-PAMAM was endocytosed by U87 MG cells. In vivo fluorescence imaging of U87MG tumor-bearing mice confirmed that the fluorescence intensity at glioma site of targeted group was 2.02 folds higher than that of untargeted group (**p<0.01), and glioma distribution experiment further revealed that Pep-PEG-PAMAM exhibited a significantly enhanced accumulation and improved penetration at tumor site. In conclusion, Pep-1 modified PAMAM was a promising nanocarrier for targeted delivery of brain glioma.

The effect of recombinant sTGFß1RII and sIL13Rα2 receptor proteins on schistosomiasis japonica, hepatic fibrosis and signal transduction in a mouse model of schistosome disease.

This study was designed to investigate the effect of recombinant sTGFß1RII and sIL13Rα2 receptor proteins on schistosomiasis japonica, hepatic fibrosis and the expression of SMAD3 and STAT6. The proteins sTGFß1RII and sIL13Rα2 were expressed in Escherichiacoli, purified using affinity chromatography and characterized by Western blotting. Female BALB/C mice (48) were randomly divided into eight groups and infected with Schistosoma japonicum. Five weeks after infection, test groups were injected with the recombinant proteins at different doses. Eight weeks after infection, lung and hepatic tissue samples were obtained and stained with hematoxylin and eosin (HE) and Masson's trichrome. Immunohistochemical staining was used to detect the expression of SMAD3 and STAT6. The recombinant proteins sTGFß1RII and sIL13Rα2 were successfully expressed, purified, and characterized. The granuloma area, hepatic hydroxyproline (HYP) level and hepatic fibrosis of the protein therapeutic groups were significantly smaller than those of the positive control group (P<0.01). Treatment with sTGFß1RII was more effective when the protein was administered for 4weeks rather than 2 (P<0.01). Hepatic fibrosis in the groups using a low dose of protein sTGFß1 was lower that of the combination group (P<0.05). The expression level of STAT6 was significantly lower in groups treated with sIL13Rα2 than in groups not treated with the protein (P<0.01). The recombinant proteins TGFß1RII and sIL13Rα2 were able to decrease granuloma area and hepatic fibrosis in schistosomiasis japonica, and also reduced the expression of the signal transduction proteins SMAD3 and STAT6. The proteins were more effective when used in combination than when applied singly.

Effect of interleukin 13 on bronchial hyperresponsiveness and the bronchoprotective effect of beta-adrenergic bronchodilators and corticosteroids.

BACKGROUND: Fluticasone affects airway bronchial hyperresponsiveness (BHR) and enhances bronchodilation and bronchoprotection induced by beta-adrenergic agonists. Interleukin 13 (IL-13), however, induces BHR. OBJECTIVE: To test the hypotheses that fluticasone inhibits BHR after either allergen sensitization or IL-13 administration and that fluticasone restores the bronchodilation and bronchoprotective effects of beta-agonists. METHODS: The BHR to methacholine induced by IL-13 or ovalbumin was determined in BALB/c mice, and the provocation concentration of methacholine that caused an increase in enhanced pause in expiration of 200% (PC200) was calculated. We compared this response to methacholine in control mice with the response after treatment with IL-13 receptor alpha 2-IgGFc fusion protein (IL-13R alpha 2) (an IL-13 blocker), fluticasone, albuterol, salmeterol, fluticasone-albuterol, and fluticasone-salmeterol. RESULTS: IL-13R alpha 2 (PC200, 17.59) completely blocks the BHR-induced effects of IL-13 (PC200, 7.28; P < .005). After IL-13 therapy (PC200, 5.90; P < .005), 1 mg/mL of albuterol (PC200, 3.38; P = .33), fluticasone (PC200, 4.59; P = .40), or fluticasone plus 50 microg/mL of salmeterol (PC200, 5.59; P = .11) showed no significant bronchoprotection. In nonsensitized mice, fluticasone plus 0.25 microg/mL of salmeterol (PC200, 25.90; P < .005) showed significantly greater bronchoprotection than did salmeterol alone (PC200, 11.08; P = .26). Fluticasone plus 0.3 mg/mL of albuterol and fluticasone plus 1 mg/mL of albuterol were significantly more protective than was fluticasone or albuterol alone in ovalbumin-sensitized mice. CONCLUSIONS: The protective effects of fluticasone, beta-agonists, and fluticasone plus beta-agonists are significantly less in IL-13-treated mice than in nonsensitized or ovalbumin-sensitized mice.

IL-13 Ralpha2-mediated interleukin-13 neutralization represses in vivo progressive growth of a T-cell lymphoma.

Dalton's lymphoma (DL) is a T-cell lymphoma of spontaneous origin, characterized by highly invasive and malignant nature, killing the host in a very short period of life span. DL-bearing host is reflected by very high titer of IL-13 in serum. Therefore, we hypothesized that over expression of IL-13 may greatly affect the growth of DL-cells in a tumor-bearing host. In this study, to assess the involvement of IL-13 in DL-cell progression, we have blocked the IL-13 activity/signalling by the systemic delivery of non-signaling decoy receptor IL-13 Ralpha2, and IL-13 level vs DL-cell proliferation were measured. We observed that systemic delivery of IL-13 Ralpha2 inhibits the DL-cell progression in much extent and enhances the survival and longevity of DL-bearing mice. Further, this study re-inforce the therapeutic advantage of IL-13 Ralpha2 in a T-cell lymphoma tumor system.