Emerging role of Unfolded Protein Response (UPR) mediated proteotoxic apoptosis in diabetes.

Background. Overexpression of the MUC5B protein is associated with idiopathic pulmonary fibrosis (IPF), but little information is available regarding the pathogenic effects and regulatory mechanisms of overexpressed MUC5B in IPF. Main Body. The overexpression of MUC5B in terminal bronchi and honeycomb cysts produces mucosal host defensive dysfunction in the distal airway which may play an important role in the development of IPF. This review addresses the possible association of overexpression of MUC5B, with MUC5B promoter polymorphism, MUC5B gene epigenetic changes, effects of some transcriptional factors, and inflammatory mediators in IPF. In addition, the associated signaling pathways which may influence the expression of MUC5B are also discussed. Conclusion. This work has important implications for further exploration of the mechanisms of overexpression of MUC5B in IPF, and future personalized treatment.

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The Possible Pathogenesis of Idiopathic Pulmonary Fibrosis considering MUC5B

Asthma has long attracted extensive attention because of its recurring symptoms of reversible airflow obstruction, airway hyperresponsiveness (AHR) and airway inflammation. Although accumulating evidence has enabled gradual increases in understanding of the pathogenesis of asthma, many questions regarding the mechanisms underlying asthma onset and progression remain unanswered. Recent advances delineating the potential functions of endoplasmic reticulum (ER) stress in meeting the need for an airway hypersensitivity response have revealed critical roles of unfolded protein response (UPR) pathways in asthma. In this review, we highlight the roles of ER stress and UPR activation in the etiology, pathogenesis and treatment of asthma and discuss whether the related mechanisms could be targets for therapeutic strategies.

Update on the role of endoplasmic reticulum stress in asthma.

Higenamine alleviates allergic rhinitis by activating AKT1 and suppressing the EGFR/JAK2/c-JUN signaling.

Background and Objectives：Among the numerous mucin genes, MUC8 is regarded as one of the most important mucin genes which are related with upper airway disease such as a nasal polyp. 15-Deoxy-delta 12,14 -prostaglandin J2 (15d-PGJ2), the most recently discovered prostaglandin, has been known to have multiple cellular functions, including anti-inflammatory and cytoprotective effects. However, the effect of 15d-PGJ2 on mucin gene expression or mucin production has not yet been investigated. The purpose of this study was to determine the effect of 15d-PGJ2 on interleukin-1β (IL-1β)-induced MUC8 gene expression and mucin secretion in the cultured NCI-H292 cells and human nasal polyp epithelial cells. Subjects and Method：The MUC8 mRNA levels were analyzed by reverse transcription-polymerase chain reaction (RT-PCR) and MUC8 mucin levels were measured using an enzyme-linked immunosorbent assay (ELISA) in the cultured epithelial cells stimulated by IL-1β. 15d-PGJ2 was added 1 hour before stimulation. Results：15d-PGJ2 attenuated the IL-1β-induced MUC8 mRNA expression and mucin secretion with a dose-dependent pattern in both cultured NCI-H292 cells and human nasal polyp epithelial cells. Conclusion：These results suggest that 15d-PGJ2 may be considered as an effective agent for the control of airway mucus hypersecretion through the down-regulation of MUC8 gene. (Korean J Otorhinolaryngol-Head Neck Surg 2008;51:435-40)

in the Human Airway Epithelial Cells

Objectives Endoplasmic reticulum (ER) stress is known to be associated with inflammatory airway diseases, and three major transmembrane receptors: double-stranded RNA-activated protein kinase-like ER kinase, inositol requiring enzyme 1, and activating transcription factor 6 (ATF6) play important roles in ER stress-related proinflammatory signaling. However, the effects of ER stress and these three major signaling pathways on the regulation of the production of airway mucins in human nasal airway epithelial cells have not been elucidated. Methods In primary human nasal epithelial cells, the effect of tunicamycin (an ER stress inducer) and 4-phenylbutyric acid (4-PBA, ER stress inhibitor) on the expression of MUC5AC and MUC5B was investigated by reverse transcriptase-polymerase chain reaction, real-time polymerase chain reaction, enzyme immunoassay, and immunoblot analysis. Small interfering RNA (siRNA) transfection was used to identify the mechanisms involved. Results Tunicamycin increased the expressions of MUC5AC and MUC5B and the mRNA expressions of ER stress-related signaling molecules, including spliced X-box binding protein 1 (XBP-1), transcription factor CCAAT-enhancer-binding protein homologous protein (CHOP), and ATF6. In addition, 4-PBA attenuated the tunicamycin-induced expressions of MUC5AC and MUC5B and the mRNA expressions of ER stress-related signaling molecules. Furthermore, siRNA knockdowns of XBP-1, CHOP, and ATF6 blocked the tunicamycin-induced mRNA expressions and glycoprotein productions of MUC5AC and MUC5B. Conclusion These results demonstrate that ER stress plays an important role in the regulation of MUC5AC and MUC5B via the activations of XBP-1, CHOP, and ATF6 in human nasal airway epithelial cells.

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Endoplasmic Reticulum Stress Induces MUC5AC and MUC5B Expression in Human Nasal Airway Epithelial Cells.

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-1β (IL-1β)-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-1β-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-1βinduced 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. (Korean J Otorhinolaryngol-Head Neck Surg 2007; 50:784-8)

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

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

Min Han Kim

Papers

Endoplasmic Reticulum Stress Induces MUC5AC and MUC5B Expression in Human Nasal Airway Epithelial Cells.

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

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