Histone deacetylase activity is a novel target for epithelial barrier defects in patients with eosinophilic chronic rhinosinusitis with nasal polyps.

BACKGROUND: Studies have independently indicated that eosinophils and histone deacetylases (HDACs) may compromise the integrity of the epithelial barrier in nasal polyps; however, the underlying mechanisms are not clear. In this study, we aimed to investigate the role of eosinophilia and HDACs in regulation of tight junctions (TJs) and nasal epithelial barrier integrity in chronic rhinosinusitis with nasal polyps (CRSwNP) patients. METHODS: Expression of mRNAs and proteins of TJs and HDACs of biopsy specimens and air-liquid interface (ALI) human nasal epithelial cell cultures (HNECs) from eosinophilic and noneosinophilic CRSwNP patients and healthy controls was assessed. The ALI HNECs were also assessed for changes in transepithelial electrical resistance (TER) and paracellular flux of fluorescein isothiocyanate (FITC)-labelled dextran. Meanwhile, the assessments for the effect of HDAC inhibitor in eosinophilic nasal polyps were also conducted. RESULTS: Decreased TER and increased paracellular flux of FITC-labelled dextran in the ALI cultures were found in both eosinophilic and noneosinophilic CRSwNP, along with irregular, patchy and reduced expression of claudin-1, 4, 7, occludin, zonula occludens (ZO)-1 and ZO-2 and increased expression of HDAC1, 9 and SIRT7 for both ALI culture cells and biopsy specimens, especially for the eosinophilic CRSwNP group. Treatment of eosinophilic CRSwNP ALI-HNECs with an HDAC inhibitor improved the TJs expression and epithelial barrier integrity. CONCLUSIONS: Our data suggest that eosinophilia and HDACs influence epithelial barrier function in CRSwNP patients by regulating TJ protein expression. Targeting HDACs with specific inhibitors may be a potential treatment option for patients with eosinophilic CRSwNP.

Comparative study on characteristics of mandarin peel extracts by biological processing.

Mandarin peel is a by-product from mandarin canning industry containing multiple functional substances with useful properties such as antibacterial and antioxidant activities. To evaluate the effect of bioprocessing, fresh mandarin peels were fermented by Rhizopus stolonifer JP13 for 4 days and then the peels' antioxidant and antimicrobial activities were tested. The flavonoiuds, hesperidin and VC contents in dry peels were also determined. The data showed that the fermented mandarin peels had promoted antibacterial activity against Escherichia coli, Staphylococcus aureus, Aspergillus flavus, and Candida albicans. An increased scavenging effect on free radicals, with 73.0% of·OH scavenging activities were obtained when compared with fresh mandarin peels. We also observed a significant increase on content of flavonoid (334%) and hesperindin (253.7%), a reduced scavenging effect on O2- free radicals (13.94%), and a decrease content of VC (13.7%). The presaging of mandarin peels by Rhizopus stolonifer JP13 strain will promote the functional activities of mandarin peels and accelerate the process of manufacture Citri Reticulatae Pericarpium.

Isoforskolin downregulates proinflammatory responses induced by Borrelia burgdorferi basic membrane protein A.

The plant Coleus forskohlii is distributed primarily in India, Thailand, China, Egypt and Brazil and has a history of use in the treatment of multiple diseases. Isoforskolin (ISOF) is the principle active component of C. forskohlii native to China and has previously been studied for its biological effects. The aim of the present study was to evaluate the effect of ISOF on the proinflammatory responses induced by recombinant Borrelia burgdorferi basic membrane protein A (rBmpA). In in vitro experiments, the proinflammatory effects of rBmpA and the anti-inflammatory function of ISOF were evaluated in murine macrophages, human macrophages and dendritic cells by detecting the transcription and expression of tumor necrosis factor (TNF)-α and interleukin (IL)-6. In in vivo experiments, mean arthritis index and X-ray and histopathological examinations were used to verify the role of ISOF in experimental Lyme arthritis in mice. The results indicated that rBmpA, which induced the transcription and expression of TNF-α and IL-6, activated proinflammatory responses in murine macrophages, human macrophages and dendritic cells. In turn, ISOF downregulated the transcription and expression of TNF-α and IL-6 induced by rBmpA. Additionally, the in vivo experiments demonstrated that ISOF could also inhibit the symptoms of experimental Lyme arthritis. These results suggest that ISOF may have a potential application as an anti-inflammatory agent for the treatment of Lyme arthritis.

[Involvement of MAPK signal transduction pathways in regulating the expression of glucocorticoid receptor isoforms in nasal polyp epithelia in vitro].

OBJECTIVE: To explore the upstream signal transduction mechanism responsible for the decrease of the ratio of the two glucocorticoid receptor (GR) subunits (GRα and GRß) in nasal polyp in vitro. METHODS: The GRα/GRß decrease cell model was established by lipopolysaccharide (LPS)-induced human nasal epithelia (HNE) of nasal polyp in vitro. Changes in the protein and mRNA expression of GRα, GRß and the key enzymes in the p38MAPK, ERK and JNK signal pathways were measured, respectively, before and after being induced with different doses of LPS and specific inhibitors of p38MAPK, JNK and ERK. SPSS 16.0 software (Analysis of variance, ANOVA) was used to analyze the data. RESULTS: With the LPS induction, the GRα/GRß ratio declined in both a time-dependent manner and a concentration-dependent manner in HNE, which demonstrated the successful establishment of a GRα/GRß decrease model in vitro. After cultured HNE were induced with the same set of LPS, the p38MAPK, ERK and JNK signal pathways were also activated. The mRNA expression of p38MAPK and JNK in each LPS-induced group (17.14 ± 1.50, 22.34 ± 2.78, 30.12 ± 1.07; 2.51 ± 0.13, 3.79 ± 0.67, 4.41 ± 0.83; 25.62 ± 1.77, 31.33 ± 1.97, 37.25 ± 2.46) was significantly higher than that (7.39 ± 0.31, 2.04 ± 0.34, 2.38 ± 0.35) in the control group (χ² value was 15.347, 18.331, 14.671, all P < 0.01). Either a specific inhibitor (SB203580) of the p38MAPK pathway or a specific inhibitor (SP600125) of the JNK pathway increased the GRα/GRß ratio at the meantime of inhibiting their pathways. SB203580 exhibited a much stronger increase effect on GRα/GRß ratio than SP600125. The specific inhibitors (PD98059) of ERK had no influence on the expression of GR isoforms. CONCLUSIONS: The above results demonstrated that the decrease of GRα/GRß ratio in HNE induced by LPS in vitro is mediated through the p38MAPK and JNK signal pathways. It is possible to improve the treatment effect of GC resistance in nasal polyp by targeting these specific signal pathways.