Interferon-alpha upregulates gene expression of aquaporin-5 in human parotid glands.
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.
Smith
J K
JK
Department of Internal Medicine, James H. Quillen College of Medicine, Johnson City, TN 37614-0622, USA. smithj@etsu.edu
Siddiqui
A A
AA
Modica
L A
LA
Dykes
R
R
Simmons
C
C
Schmidt
J
J
Krishnaswamy
G A
GA
Berk
S L
SL
D000284:Administration, Oral; D051402:Aquaporin 5; D020346:Aquaporins / Q000235:genetics*; D002478:Cells, Cultured; D004353:Drug Evaluation, Preclinical; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D010306:Parotid Gland / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation
C496036:AQP5 protein, human; D051402:Aquaporin 5; D020346:Aquaporins; D016898:Interferon-alpha; D008565:Membrane Proteins