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

Aquaporins are a family of homologous membrane proteins that function as hi ghly selective water channels. Aquaporin-5 (AQP5) is uniquely present in la crimal and salivary glands, where it accounts for normal tear and saliva pr oduction. We tested the hypothesis that orally administered human interfero n-alpha (HuIFN-alpha) benefits persons with xerostomia by augmenting the pr oduction of AQP5 protein by parotid gland epithelium. Cells from three huma n parotid glands were cultured with and without human lymphoblastoid IFN-al pha, and assayed for AQP5 mRNA levels by reverse transcriptase polymerase c hain reaction (RT-PCR), and AQP5 protein levels by Western blot. Intracellu lar localization of AQP5 protein was done using confocal microscopy, The fu nctional integrity of the glandular tissue was confirmed by RT-PCR analysis of alpha-amylase 1 and basic proline-rich protein transcripts. AQP5 was co nstitutively expressed in human parotid gland tissue, with AQP5 protein res tricted to the plasma membranes and cytoplasmic vesicles of acinar cells. I FN-alpha augmented AQP5 transcription and protein production in a concentra tion-dependent manner, and increased the size of intensity of staining of A QP5-containing cytoplasmic vesicles in acinar cells, We conclude that IFN-a lpha upregulates AQP5 gene expression in human parotid acinar cells in vitr o. To our knowledge, this is the first demonstration that IFN-alpha regulat es the gene expression of an aquaporin.