Curcumin pretreatment prevents butyrate-induced cell death and release of damage-associated molecular patterns on gingival epithelial Ca9-22 cells

Abstract

Objectives

Exposure of gingival epithelial cells to butyrate, a short-chain fatty acid produced by dental plaque bacteria, cause cell death and subsequent damage-associated molecular pattern (DAMP) release. We investigated the effects of curcumin, a polyphenol extracted from turmeric, on butyrate-induced human gingival epithelial Ca9-22 cell death and DAMP release.

Methods

Ca9-22 cells were pretreated with curcumin before butyrate exposure. Cell death was quantified using SYTOX green dye, and histone H3 acetylation was analyzed by Western blot. Conditioned media were collected to detect DAMPs by Western blot. We also assessed the effects of the histone acetyltransferase (HAT) inhibitor C646, instead of curcumin, on butyrate-induced cell death, DAMP release, and histone H3 acetylation, and examined the effects of curcumin pretreatment on cell death, DAMP release, and histone H3 acetylation induced by the histone deacetylase (HDAC) inhibitors, valproate and suberoylanilide hydroxamic acid (SAHA).

Results

Curcumin pretreatment attenuated butyrate-induced Ca9-22 cell death, histone H3 acetylation, and release of the DAMPs. The C646 also attenuated butyrate-induced cell death, DAMP release, and histone H3 acetylation. Curcumin also suppressed cell death, DAMP release, and histone H3 acetylation triggered by the HDAC inhibitors (valproate and SAHA).

Conclusions

Curcumin pretreatment ameliorated butyrate-induced histone H3 acetylation, cell death, and DAMP release. As elevated histone acetylation by HDAC inhibitors correlates with increased cell death, while reduced acetylation by a HAT inhibitor is associated with their attenuation, protective effects of curcumin against butyrate-induced Ca9-22 cell death and subsequent DAMP release may occur via suppression of histone acetylation.