TNF-α inhibits aquaporin 5 expression in human salivary gland acinar cells via suppression of histone H4 acetylation.
Bottom Line: The mechanisms underlying these reductions remain unclear.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.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.
Affiliation: Department of Oral Medicine, Institute of Health Biosciences, The University of Tokushima Graduate Faculty of Dentistry, Tokushima, Japan.Show MeSH
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Mentions: Global levels of histone acetylations upon treatment with TNF-α were examined by Acetylation Assay Kits and Western blotting with antibodies specific for acetylated histone H4 (lysines 5, 8, 12, 16) and total histone H4. As shown in Figure 5A, TNF-α treatment of NS-SV-AC cells significantly suppressed the acetylation levels of histone H4, but not of histone H3. When ductal (NS-SV-DC) cells were used as a control, histone H4 acetylation level was not affected by TNF-α treatment. In addition, we determined levels of acetylated histone H4 protein by Western blot analysis. As shown in Figure 5B, treatment with TNF-α decreased levels of acetylated histone H4. The steady-state levels of histone H4 did not change significantly under a variety of conditions. In addition, fluorescence-microscopic examination revealed that nuclear staining of acetylated histone H4 was evident in control cells, however, reduced expression of acetylated histone H4 was detected in TNF-α-treated cells (Fig. 6). When primary antibody was omitted, no positive staining was observed (data not shown).
Affiliation: Department of Oral Medicine, Institute of Health Biosciences, The University of Tokushima Graduate Faculty of Dentistry, Tokushima, Japan.