Effect of the fungal immunomodulatory protein FIP-fve on airway inflammation and cytokine production in mouse asthma model.

The allergy is dependent on the balance between Th1 and Th2. The fungal immunodulatory protein (FIP-fve) was isolated from Flammulina velutipes. FIP-fve has been demonstrated to skew the response to Th1 cytokine production. We investigated whether oral administrations of FIP-fve inhibited allergen (OVA)-induced chronic airway inflammation in the mouse asthma model. After intranasal challenge with OVA, the airway inflammation and hyperresponsiveness were determined by bronchoalveolar lavage fluid (BALF) analysis and ELISA assay. Both pre-treated and post-treated with FIP-fve suppressed the airway hyperresponsiveness by methacholine challenge and significantly decreased the number of infiltrating inflammatory cells and Th2 cytokines in bronchoalveolar lavage fluid (BALF) and serum compared with the OVA sensitized mice. In addition, FIP-fve reduced OVA-specific IgE levels in serum. FIP-fve markedly alleviated the OVA-induced airway hyperresponsiveness (AHR) to inhaled methacholine. Based on lung histopathological studies using hematoxylin and Liu's staining, FIP-fve inhibited inflammatory cell infiltration compared with the OVA-sensitized mice. Oral FIP-fve had an anti-inflammatory effect on OVA-induced airway inflammations and might posses the potential for alternative therapy for allergic airway diseases.

Effect of combination treatment with Lactobacillus rhamnosus and corticosteroid in reducing airway inflammation in a mouse asthma model.

BACKGROUND: Asthma is a complex multifactorial chronic airway inflammatory disease with diverse phenotypes and levels of severity and is associated with significant health and economic burden. In a certain population of asthma patients, the symptoms cannot be well controlled with steroid. There has been long standing interest in the use of probiotics for treating allergic diseases. The purpose of this study is to investigate whether the combination of Lactobacillus rhamnosus GG (LGG) with prednisolone could reduce the dosage of glucocorticoid in controlling airway inflammation in a murine model for allergic asthma. MATERIAL AND METHODS: We used Der p 2-sensitized asthma model in female BALB/c mice. The animals were treated with 75 µl or 50 µl oral prednisolone or combination treatment of these two doses of oral prednisolone with LGG. Airway hyperresponsiveness, serum specific IgE/IgG1/IgG2a, infiltrating inflammatory cells in lung and cytokines were assessed. RESULTS: Compared to 75 µl prednisolone, a lower dose of prednisolone with 50 µl was less satisfactory in suppressing airway hyperresponsives, serum IgE and IgG1, Th2 cytokines and inflammatory cytokines such as IL-6, IL-8 and IL-17 as well as infiltrating inflammatory cells. However, combination of 50 µl prednisolone and LGG decreased airway resistance and serum IgE and IgG1, inhibited the production of IL-4, IL-5, IL-6, IL-8, IL-13 and IL-17, upregulated serum IgG2a and enhanced Th1 immune response. CONCLUSIONS: LGG may reduce the dosage of prednisolone and thus may be beneficial in the treatment of asthma.

Effect of Lactobacillus rhamnosus GG immunopathologic changes in chronic mouse asthma model.

BACKGROUND: Asthma is a heterogeneous inflammatory disorder of the airway. A Th2 response usually contributes to high levels of allergen-specific IgE and eosinophilic airway inflammation. Several findings have demonstrated that neutrophils, not eosinophils, are the major inflammatory cells in chronic asthma patients with steroid-resistance. Lactobacillus rhammosus GG (LGG) exhibits anti-inflammatory properties on OVA-induced acute airway inflammation. OBJECTIVE: We hypothesized that orally administrated LGG should reduce airway remodeling in chronic experimental models. METHODS: Female Balb/c mice were sensitized with OVA. LGG was used to investigate whether oral administrations of LGG inhibited OVA-induced airway inflammation in a chronic asthma model and the different intervention times between LGG pre-treatment and post-treatment groups. BALF was analyzed with Liu's stain and ELISA assay. Lung histopathology was assayed with HE, IHC and Masson's trichrome staining. Lung tissues were assayed with PCR (T-bet, GATA3, RORrt and Foxp3). Many cytokines were detected in the serum and BALF. RESULTS: LGG significantly decreased the number of infiltrating inflammatory cells. We also found that the oral LGG group suppressed not only Th2 cytokine, but also IL-17, TNF-α and HMGB1 in the BALF levels. However, GATA3 and RORrt decreased significantly in the RNA level in the LGG groups, but the T-bet and Foxp3 increased in the RNA level. CONCLUSIONS: LGG not only had anti-inflammatory effects on OVA-induced airway inflammation, but also improved airway remodeling and collagen expression in the chronic asthma mouse model. Moreover, LGG might be an additional or supplementary therapy for allergic airway diseases.

Fungal immunomodulatory protein-fve could modulate airway remodel through by affect IL17 cytokine.

BACKGROUND: Asthma is one of the most common allergic diseases. Our previous studies have reported that FIP-fve in acute allergic mouse model can reduce inflammation, improve the balance of the Th1/Th2 system. However, the effects of reducing airway remodeling on FIP-fve is still unknown. OBJECTIVE: We hypothesized that orally administrated FIP-fve should be able to reduce airway remodeling in chronic allergic models. METHODS: The chronic asthma animal model was established with 6-8 weeks female Balb/c mice. After intranasal challenges with OVA, the airway inflammation and AHR were determined by a BUXCO system. BALF was analyzed with Liu's stain and ELISA assay. Lung histopathologic changes and Collagen deposition were assayed with H&E, Masson's trichrome and IHC stain. RESULTS: FIP-fve significantly decreased the number of infiltrating inflammatory cells and Th2 cytokines and increased Th1 cytokines in BALF and serum compared with the OVA sensitized mice. FIP-fve had a better effect than corticosteroid could reduce infiltrating cells in lung especially neutrophils and eosinophils. We also found that the oral FIP-fve group suppressed IL-17 and enhanced IL-22 in the serum and BALF. In addition, oral FIP-fve decreased MMP9 expression, collagen expression and airway remodeling in lung tissues. CONCLUSION: FIP-fve had anti-inflammatory effects on OVA-induced airway inflammation and an effect to inhibited Th17 cells to reduced airway remodeling and collagen expression. Moreover, FIP-fve might be a potential alternative therapy for allergic airway diseases.

Effects of immunomodulatory supplementation with Lactobacillus rhamnosus on airway inflammation in a mouse asthma model.

BACKGROUND: Asthma is a common allergic disease. In previous studies, probiotics improved the balance of intestinal microbes, reduced inflammation, and promoted mucosal tolerance. This study investigated whether oral administrations of Lactobacillus rhamnosus GG (LGG) inhibited allergen (ovalbumin or OVA)-induced airway inflammation in a mouse asthma model. METHODS: The allergy/asthma animal model in this study was sensitization with OVA. After intranasal challenge with OVA, the airway inflammation and hyper-responsiveness were determined by a Buxco system, bronchoalveolar lavage fluid analysis with Liu stain, and enzyme-linked immunosorbent assay. Histopathologic changes in the lung were detected by hematoxylin and eosin staining and immunohistochemistry staining. RESULTS: Both pre- and post-treatment with LGG suppressed the airway hyper-responsiveness to methacholine and significantly decreased the number of infiltrating inflammatory cells and Th2 cytokines in bronchoalveolar lavage fluid and serum compared with the OVA-sensitized mice. In addition, LGG reduced OVA-specific IgE levels in serum. Oral LGG decreased matrix metalloproteinase 9 expression in lung tissue and inhibited inflammatory cell infiltration. CONCLUSION: LGG had an anti-inflammatory effect on OVA-induced airway inflammation and might be an additional or supplementary therapy for allergic airway diseases.

Nobiletin inhibits human osteosarcoma cells metastasis by blocking ERK and JNK-mediated MMPs expression.

Nobiletin, a polymethoxyflavone, has a few pharmacological activities, including anti-inflammation and anti-cancer effects. However, its effect on human osteosarcoma progression remains uninvestigated. Therefore, we examined the effectiveness of nobiletin against cellular metastasis of human osteosarcoma and the underlying mechanisms. Nobiletin, up to 100 µM without cytotoxicity, significantly decreased motility, migration and invasion as well as enzymatic activities, protein levels and mRNA expressions of matrix metalloproteinase (MMP)-2 and MMP-9 in U2OS and HOS cells. In addition to inhibition of extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK), the inhibitory effect of nobiletin on the DNA-binding activity of the transcription factor nuclear factor-kappa B (NF-κB), cAMP response element-binding protein (CREB), and specificity protein 1 (SP-1) in U2OS and HOS cells. Co-treatment with ERK and JNK inhibitors and nobiletin further reduced U2OS cells migration and invasion. These results indicated that nobiletin inhibits human osteosarcoma U2OS and HOS cells motility, migration and invasion by down-regulating MMP-2 and MMP-9 expressions via ERK and JNK pathways and through the inactivation of downstream NF-κB, CREB, and SP-1. Nobiletin has the potential to serve as an anti-metastatic agent for treating osteosarcoma.

A trial of adding Lactobacillus johnsonii EM1 to levocetirizine for treatment of perennial allergic rhinitis in children aged 7-12 years.

BACKGROUND: Supplementary consumption of probiotics may temporarily alter the intestinal microflora of infants and children, thereby preventing and treating allergic disorders. OBJECTIVE: To compare the clinical efficacy of levocetirizine with that of levocetirizine plus Lactobacillus johnsonii EM1 (Lj EM1) for treating perennial allergic rhinitis (PAR) in children. METHODS: Sixty-three children aged 7-12 years fulfilled the entry criteria for the study and had moderate to severe PAR of at least 1 year's duration. The treatment followed a randomized, open-label crossover design: all subjects were randomized to 2 crossover treatment regimens of levocetirizine with Lj EM1 (group 1) or levocetirizine alone (group 2) for 12 weeks; subsequently, treatments were reversed for a further 12 weeks. The effects of the 2 regimens were compared using the Pediatric Rhinoconjunctivitis Quality of Life Questionnaire (PRQLQ) and the total symptom score (TSS) from diary cards. The parameters evaluated were nasal peak expiratory flow rate (nPEFR), FVC, FEV1, serum immunoglobulin E (IgE), mite-specific IgE, eosinophilic cationic protein (ECP), resistin, blood eosinophils, eosinophil percentage in nasal smears, IL-4, IL-10, interferon-γ (IFN-γ), and transforming growth factor-ß (TGF-ß). RESULTS: After the first 12 weeks of treatment, TSS in both groups had improved progressively compared with that in the run-in period. Both groups had improved TSS at weeks 4, 8, and 12 (P<0.05), and group 1 was more efficacious than group 2 at week 4 (P=0.014), week 8 (P=0.011), and week 12 (P<0.009). During the second 12-week period, group 2 showed continual and progressive improvement, while group 1 did not. The PRQLQ scores were significantly decreased in both groups (P<0.05), but there was no statistically significant difference between the 2 groups (P=0.446). The eosinophil percentage in nasal smears decreased in both groups compared with that in the run-in period, and significant differences were detected in groups 2 and 1at 16 and 24 weeks of treatment, respectively (P<0.05). Both groups showed significant improvement in nPEFR at weeks 4, 8, 12, 16, and 24 (P<0.01), and the treatment for group 1 appeared to be more efficacious than that for group 2 at weeks 12, 16, and 20 (P<0.05). FVC and FEV1 were improved in both groups at weeks 8 through 24 (P<0.05), but there was no significant difference between the 2 groups. In cytokine measurements, IFN-γ and IL-10 increased significantly and IL-4 decreased significantly in both groups, while elevation of TGF-ß was seen only in group 1 at 12 weeks (P<0.001). However, the difference in TGF-ß disappeared after 24 weeks treatment. There was no difference in serum resistin levels. No serious adverse events were recorded in either treatment group. CONCLUSION: The 24-week, 2-phase, crossover treatment program showed that levocetirizine plus Lj EM1 was more effective for PAR than levocetirizine and that this difference persisted for at least 3 months after discontinuation of Lj EM1.