Interferon-alpha upregulates gene expression of aquaporin-5 in human parotid glands

• Published in: Journal of interferon & cytokine research Vol. 19; no. 8; pp. 929 - 935
• Main Authors: Smith, J K, Siddiqui, A A, Modica, L A, Dykes, R, Simmons, C, Schmidt, J, Krishnaswamy, G A, Berk, S L
• Format: Journal Article
• Language: English
• Published: United States Mary Ann Liebert, Inc 01.08.1999
• Subjects: Administration, Oral; Aquaporin 5; Aquaporins - genetics; Cells, Cultured; Drug Evaluation, Preclinical; Gene Expression - drug effects; Humans; Interferon-alpha - therapeutic use; Male; Membrane Proteins; Middle Aged; Parotid Gland - cytology; Parotid Gland - drug effects; Parotid Gland - metabolism; Reverse Transcriptase Polymerase Chain Reaction; Up-Regulation
• ISSN: 1079-9907; 1557-7465
• DOI: 10.1089/107999099313479

Aquaporins are a family of homologous membrane proteins that function as highly selective water channels. Aquaporin-5 (AQP5) is uniquely present in lacrimal and salivary glands, where it accounts for normal tear and saliva production. We tested the hypothesis that orally administered human interferon-alpha (HuIFN-alpha) benefits persons with xerostomia by augmenting the production of AQP5 protein by parotid gland epithelium. Cells from three human parotid glands were cultured with and without human lymphoblastoid IFN-alpha, and assayed for AQP5 mRNA levels by reverse transcriptase polymerase chain reaction (RT-PCR), and AQP5 protein levels by Western blot. Intracellular localization of AQP5 protein was done using confocal microscopy. The functional integrity of the glandular tissue was confirmed by RT-PCR analysis of alpha-amylase 1 and basic proline-rich protein transcripts. AQP5 was constitutively expressed in human parotid gland tissue, with AQP5 protein restricted to the plasma membranes and cytoplasmic vesicles of acinar cells. IFN-alpha augmented AQP5 transcription and protein production in a concentration-dependent manner, and increased the size of intensity of staining of AQP5-containing cytoplasmic vesicles in acinar cells. We conclude that IFN-alpha upregulates AQP5 gene expression in human parotid acinar cells in vitro. To our knowledge, this is the first demonstration that IFN-alpha regulates the gene expression of an aquaporin.