Effect of Pepsin on Laryngeal Stress Protein (Sep70, Sep53, and Hsp70) Response: Role in Laryngopharyngeal Reflux Disease
Autor: | Nikki Johnston, Mark O. Lively, Peter C. Belafsky, Gregory N. Postma, Peter W. Dettmar, Jamie A. Koufman, Martin A. Birchall |
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Rok vydání: | 2006 |
Předmět: |
Adult
Male Larynx medicine.medical_specialty Pathology Adolescent Swine Blotting Western In Vitro Techniques Organ culture Gastroenterology 03 medical and health sciences Laryngopharyngeal reflux 0302 clinical medicine Gastrointestinal Agents Pepsin Heat shock protein Internal medicine Carcinoma Animals Humans Medicine HSP70 Heat-Shock Proteins 030223 otorhinolaryngology Cells Cultured Heat-Shock Proteins Aged Microscopy Confocal biology business.industry General Medicine Middle Aged medicine.disease Pepsin A Squamous carcinoma Hsp70 medicine.anatomical_structure Otorhinolaryngology 030220 oncology & carcinogenesis Gastroesophageal Reflux biology.protein Female business Biomarkers |
Zdroj: | Annals of Otology, Rhinology & Laryngology. 115:47-58 |
ISSN: | 1943-572X 0003-4894 |
Popis: | Objectives: The objectives of this study were to define the conditions that give rise to a stress protein response in laryngeal epithelium and to investigate whether and how stress protein dysfunction contributes to reflux-related laryngeal disease. Methods: Western analysis was used to measure stress protein (squamous epithelial proteins Sep70 and Sep53 and heat shock protein Hsp70) and pepsin levels in esophageal and laryngeal tissue specimens taken from both normal control subjects and patients with pH-documented laryngopharyngeal reflux (LPR) who had documented lesions, some of whom had laryngeal cancer. A porcine organ culture model was used to examine the effects of low pH and pepsin (0.1% porcine pepsin A) on stress protein levels. A laryngeal squamous carcinoma (FaDu) cell line was used to examine uptake of human pepsin 3b-tetramethyl-5 and -6 isothiocyanate. Results: Sep70, Sep53, and Hsp70 were found to be expressed at high levels, and pepsin was not detected, in esophageal and laryngeal specimens taken from normal control subjects and in esophageal specimens taken from LPR patients. The patients with LPR were found to have significantly less laryngeal Sep70 (p = .027) and marginally less laryngeal Sep53 (p = .056) than the normal control subjects. Laryngeal Hsp70 was expressed at high levels in the LPR patients. The patients with laryngeal cancer had significantly lower levels of Sep70, Sep53 (p < .01), and Hsp70 (p < .05) than the normal control subjects. A significant association was found between the presence of pepsin in laryngeal epithelium from LPR patients and depletion of laryngeal Sep70 (p < .001). Using the organ culture model, we demonstrated that laryngeal Sep70 and Sep53 proteins are induced after exposure to low pH. However, in the presence of pepsin, Sep70 and Sep53 levels are depleted. Confocal microscopy analysis of cultured cells exposed to labeled pepsin revealed that uptake is by receptor-mediated endocytosis. Conclusions: These findings suggest that receptor-mediated uptake of pepsin by laryngeal epithelial cells, as may occur in LPR, causes a change in the normal acid-mediated stress protein response. This altered stress protein response may lead to cellular injury and thus play a role in the development of disease. |
Databáze: | OpenAIRE |
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