Butyrate Decreases ICAM-1 Expression in Human Oral Squamous Cell Carcinoma Cells

Int J Mol Sci. 2020 Feb 29;21(5):1679. doi: 10.3390/ijms21051679.

Abstract

Short-chain fatty acids (SCFA) are bacterial metabolites that can be found in periodontal pockets. The expression of adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1) within the epithelium pocket is considered to be a key event for the selective transmigration of leucocytes towards the gingival sulcus. However, the impact of SCFA on ICAM-1 expression by oral epithelial cells remains unclear. We therefore exposed the oral squamous carcinoma cell line HSC-2, primary oral epithelial cells and human gingival fibroblasts to SCFA, namely acetate, propionate and butyrate, and stimulated with known inducers of ICAM-1 such as interleukin-1-beta (IL1β) and tumor necrosis factor-alfa (TNFα). We report here that butyrate but not acetate or propionate significantly suppressed the cytokine-induced ICAM-1 expression in HSC-2 epithelial cells and primary epithelial cells. The G-protein coupled receptor-43 (GPR43/ FFAR2) agonist but not the histone deacetylase inhibitor, trichostatin A, mimicked the butyrate effects. Butyrate also attenuated the nuclear translocation of p65 into the nucleus on HSC-2 cells. The decrease of ICAM-1 was independent of Nrf2/HO-1 signaling and phosphorylation of JNK and p38. Nevertheless, butyrate could not reverse an ongoing cytokine-induced ICAM-1 expression in HSC-2 cells. Overall, these observations suggest that butyrate can attenuate cytokine-induced ICAM-1 expression in cells with epithelial origin.

Keywords: butyric acid; epithelial cells; in vitro; intercellular adhesion molecule-1; oral biology; periodontium.

MeSH terms

  • Acetates / pharmacology
  • Butyrates / pharmacology*
  • Carcinoma, Squamous Cell / drug therapy*
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / pathology
  • Cell Line, Tumor
  • Epithelial Cells / drug effects
  • Fatty Acids, Volatile / pharmacology
  • Fibroblasts / drug effects
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Intercellular Adhesion Molecule-1 / genetics*
  • Interleukin-1beta / genetics
  • Mouth Neoplasms / drug therapy*
  • Mouth Neoplasms / genetics
  • Mouth Neoplasms / pathology
  • NF-E2-Related Factor 2 / genetics
  • Propionates / pharmacology
  • Receptors, Cell Surface / genetics

Substances

  • Acetates
  • Butyrates
  • FFA2R protein, human
  • Fatty Acids, Volatile
  • ICAM1 protein, human
  • IL1B protein, human
  • Interleukin-1beta
  • NF-E2-Related Factor 2
  • NFE2L2 protein, human
  • Propionates
  • Receptors, Cell Surface
  • Intercellular Adhesion Molecule-1