Delphinidin Inhibits LPS-Induced MUC8 and MUC5B Expression Through Toll-like Receptor 4-Mediated ERK1/2 and p38 MAPK in Human Airway Epithelial Cells

OBJECTIVES: Delphinidin is one of the anthocyanidins. It is believed to have anti-inflammatory property including antioxidant, antiangiogenic, and anti-cancer properties. However, the anti-inflammatory effect of delphinidin in mucin-producing human airway epithelial cells has not been determined. Therefore, this study was conducted in order to investigate the effect and the brief signaling pathway of delphinidin in lipopolysaccharide (LPS)-induced MUC8 and MUC5B expression in human airway epithelial cells. METHODS: In mucin-producing human NCI-H292 airway epithelial cells and primary cultures of normal nasal epithelial cells, the reverse transcriptase-polymerase chain reaction (RT-PCR), real-time PCR, enzyme immunoassay were used for investigating the expressions of MUC8, MUC5, and Toll-like receptor 4 (TLR4), after LPS treatment and delphinidin treatment. And the signaling pathway of delphinidin on LPS-induced MUC8 and MUC5B expression was investigated using the RT-PCR, and immunoblot analysis. To confirm the involvement of TLR4 in LPS-induced MUC8 and MU5B expression, the cells were transfected with TLR4 siRNA. RESULTS: In NCI-H292 airway epithelial cells, LPS (100 ng/mL) significantly induced TLR4, MUC8, and MUC5B expression. TLR4 siRNA significantly blocked LPS-induced MUC8 and MUC5B mRNA expression. LPS (100 ng/mL) significantly activated the phosphorylation of extracellular signal related kinase (ERK) 1/2 and p38 mitogen-activated protein kinase (MAPK). Delphinidin (50 and 100 microM) inhibited LPS-induced TLR4, MUC8, and MUC5B expression and LPS-induced phosphorylation of ERK1/2 and p38 MAPK. In the primary cultures of normal nasal epithelial cells, delphinidin (50 and 100 microM) significantly inhibited LPS-induced TLR4, MUC8, and MUC5B gene expression. CONCLUSION: These results suggest that delphinidin attenuates LPS-induced MUC8 and MUC5B expression through the TLR4-mediated ERK1/2 and p38 MAPK signaling pathway in human airway epithelial cells. These findings indicated that delphinidin may be a therapeutic agent for control of inflammatory airway diseases.

The Clinical Correlation between Anterior Inferior Cerebellar Artery and Sudden Sensorineural Hearing Loss / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: The influence of anterior inferior cerebellar artery (AICA) loop on sudden sensorineural hearing loss (SSHL) remains controversial. The objective of this study was to evaluate the correlation between the anatomical type of AICA loop and SSHL. SUBJECTS AND METHOD: We reviewed the medical records of 69 ears from 60 patients with SSHL between January 2005 and April 2008, retrospectively. AICA loops were classified according to the Chavda classification method by magnetic resonance imaging. According to the extension depth of the loop in the internal auditory canal, it was classified as type I, II and III. The loop was classified as S (small diameter) and L (large diameter) by comparing the thickness of the loop with adjacent facial nerves. RESULTS: The predominant type of AICA loop was type I (68.1%) and type S (78.3%). There was no significant correlation between the pretreatment hearing level, extension depth and diameter. There was also no significant correlation between the rate of hearing recovery by Siegel's criteria and diameter. However, there was significant correlation between the rate of hearing recovery by Siegel's criteria and the types of the extension depth (p< 0.05). The ears with type II and III of AICA loop presented higher rates of hearing recovery by Siegel's criteria than those with type I. CONCLUSION: This study suggests that the type II and III of AICA loop may be considered a good prognostic factor in SSHL.

Effect of Macrolide on the MUC4 Gene Expression in Human Airway Epithelial Cells / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Mucin gene expression and mucin secretion are highly increased by inflammatory airway diseases such as asthma, chronic bronchitis and rhinosinusitis. Macrolide antibiotics is considered one of the effective drugs inhibiting mucus secretion for chronic bronchitis and rhinosinusitis with nasal polyp. However, the anti-secretory effect of macrolide is not clear. This study was designed to investigate whether macrolide can suppress interleukin-1beta (IL-1beta)-induced MUC4 gene expression and mucin secretion in the cultured human nasal polyp epithelial cells and NCI-H292 epithelial cells. SUBJECTS AND METHOD: Nasal polyps were obtained from 20 patients with chronic rhinosinusitis with nasal polyp during endoscopic sinus surgery. We observed the effect of roxithromycin on the IL-1beta-induced MUC4 gene and mucin secretion by reverse transcriptase-polymerase chain reaction (RT-PCR) with enzyme-linked immunosorbent assay (ELISA) method. RESULTS: Roxithromycin attenuated the IL-1beta-induced MUC4 mRNA expression and mucin secretion with a dose dependent pattern in both of the cultured human nasal polyp epithelial cells and NCI-H292 epithelial cells. CONCLUSION: This result suggests that roxithromycin may be considered as an effective anti-hypersecretory agent for its down-regulation of the MUC4 gene.