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

• Published in: Journal of cellular and molecular medicine Vol. 16; no. 8; pp. 1766 - 1775
• Main Authors: Yamamura, Yoshiko, Motegi, Katsumi, Kani, Kouichi, Takano, Hideyuki, Momota, Yukihiro, Aota, Keiko, Yamanoi, Tomoko, Azuma, Masayuki
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-08-2012; John Wiley & Sons, Inc
• Subjects: Acetylation; Acetylation - drug effects; Acinar cells; Acinar Cells - drug effects; Acinar Cells - metabolism; Antibodies; Aquaporin 5; Aquaporin 5 - genetics; Aquaporin 5 - metabolism; Autoimmune diseases; Biotechnology; Cell activation; Cells; Chromatin; Chromatin - metabolism; Cloning; DNA methylation; DNMT1 protein; Epigenetics; Exocrine glands; Fluorescent Antibody Technique; Gene expression; Gene Expression Regulation - drug effects; histone; Histone H4; Histones - metabolism; Humans; Immunoprecipitation; Membranes; Methyltransferases - metabolism; mRNA; NF-kappa B - metabolism; NF-κB protein; Original; Promoter Regions, Genetic - genetics; Proteins; Reagents; RNA, Messenger - genetics; RNA, Messenger - metabolism; Salivary gland; salivary gland acinar cells; Salivary Glands - cytology; Secretions; Sjgren's syndrome; Sjogren's syndrome; TNF‐α; Tumor Necrosis Factor-alpha - pharmacology; Tumor necrosis factor-TNF; Tumor necrosis factor-α; Water - metabolism; Grand Island; United States > US; Japan
• ISSN: 1582-1838; 1582-4934
• DOI: 10.1111/j.1582-4934.2011.01456.x

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.