TNF-α inhibits aquaporin 5 expression in human salivary gland acinar cells via suppression of histone H4 acetylation.

Publisher: Wiley-Blackwell Country of Publication: England NLM ID: 101083777 Publication Model: Print Cited Medium: Internet ISSN: 1582-4934 (Electronic) Linking ISSN: 15821838 NLM ISO Abbreviation: J Cell Mol Med Subsets: MEDLINE

Publication: Oxford, England : Wiley-Blackwell
Original Publication: Bucharest : "Carol Davila" University Press, 2000-

Acinar Cells/*metabolism ; Aquaporin 5/*genetics ; Histones/*metabolism ; Salivary Glands/*cytology ; Tumor Necrosis Factor-alpha/*pharmacology; Acetylation/drug effects ; Acinar Cells/drug effects ; Aquaporin 5/metabolism ; Chromatin/metabolism ; Fluorescent Antibody Technique ; Gene Expression Regulation/drug effects ; Humans ; Methyltransferases/metabolism ; NF-kappa B/metabolism ; Promoter Regions, Genetic/genetics ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; Water/metabolism

Sjögren's syndrome is a systemic autoimmune disease characterized by reductions in salivary and lacrimal secretions. The mechanisms underlying these reductions remain unclear. We have previously shown that TNF-α plays an important role in the destruction of acinar structures. Here we examined TNF-α's function in the expression of aquaporin (AQP) 5 in human salivary gland acinar cells. Immortalized human salivary gland acinar (NS-SV-AC) cells were treated with TNF-α, and then the expression levels of AQP5 mRNA and protein were analysed. In addition, the mechanisms underlying the reduction of AQP5 expression by TNF-α treatment were investigated. TNF-α-treatment of NS-SV-AC cells significantly suppressed the expression levels of AQP5 mRNA and protein, and reduced the net fluid secretion rate. We examined the expression and activation levels of DNA methyltransferases (Dnmts) in NS-SV-AC cells treated with TNF-α. However, no significant changes were observed in the expression or activation levels of Dnmt1, Dnmt3a or Dnmt3b. Although we also investigated the role of NF-κB activity in the TNF-α-induced suppression of AQP5 expression in NS-SV-AC cells, we detected similar TNF-α suppression of AQP5 expression in non-transfected cells and in a super-repressor form of IκBα cDNA-transfected cell clones. However, interestingly, chromatin immunoprecipitation analysis demonstrated a remarkable decrease in levels of acetylated histone H4 associated with the AQP5 gene promoter after treatment with TNF-α in NS-SV-AC cells. Therefore, our results may indicate that TNF-α inhibition of AQP5 expression in human salivary gland acinar cells is due to the epigenetic mechanism by suppression of acetylation of histone H4.
(© 2012 The Authors Journal of Cellular and Molecular Medicine © 2012 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.)

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0 (Aquaporin 5)
0 (Chromatin)
0 (Histones)
0 (NF-kappa B)
0 (RNA, Messenger)
0 (Tumor Necrosis Factor-alpha)
059QF0KO0R (Water)
EC 2.1.1.- (Methyltransferases)

Date Created: 20111007 Date Completed: 20121203 Latest Revision: 20220311

20240829

PMC3822690

10.1111/j.1582-4934.2011.01456.x

21973049