Interferon-alpha Upregulates Gene Expression of Aquaporin-5 in Human Parotid Glands

Abstract

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.

Treatment of primary sjögren's syndrome with low‐dose human interferon alfa administered by the oromucosal route: Combined phase III results

“…In another study, human parotid gland tissue cultured in the presence of low doses of IFN alfa expressed augmented aquaporin-5 (AQP5) transcription and protein production (34). Consequently, the increased UWS flow seen following IFN alfa treatment may be due to an upregulation of AQP5, with highly selective water channel proteins reported to be abnormally distributed in lacrimal and salivary glands of Sjö gren's syndrome patients (35,36).…”

Progress in Understanding Autoimmune Exocrinopathy Using the Non-obese Diabetic Mouse: An Update

“…The application resulted in decreased immune cell infiltration and increased secretory response. IFN-␣ may directly increase the density of aquaporin5 in salivary gland tissue by up-regulating the gene and the protein expression (Smith et al ., 1999). Antagonizing the effects of IFN-␥by IFN-␣ / ␤may indirectly alter the outcome of pathological changes in patients with SS, as we observed in NOD.IFN-␥ -/-mice.…”

Selective Down-Regulation of Aquaporin-1 in Salivary Glands in Primary Sjögren's Syndrome

“…Mechanisms that Lead to AQP-1 Down-Regulation Two principal mechanisms are likely to contribute to down-regulation of AQP-1 in pSS myoepithelial cells. First, studies on lung epithelium and parotid glands have demonstrated that cytokines can up-and downregulate the expression of AQP molecules (Smith et al, 1999;Towne et al, 2001), and cytokines are known to be produced in increased quantities by acinar cells and lymphocytes in pSS glands (Boumba et al, 1995;Fox et al, 1994;Grisius et al, 1997). Second, AQP-1 expression may be altered as a consequence of functional inhibition of cholinergic neurotransmission.…”