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

• Published in: International journal of molecular sciences Vol. 21; no. 5; p. 1679
• Main Authors: Magrin, Gabriel Leonardo, Di Summa, Francesca, Strauss, Franz-Josef, Panahipour, Layla, Mildner, Michael, Magalhães Benfatti, Cesar Augusto, Gruber, Reinhard
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 29.02.2020; MDPI
• Subjects: Acetic acid; Adhesion; Apoptosis; butyric acid; Cell adhesion; Cytokines; Epithelial cells; Epithelium; Fibroblasts; G protein-coupled receptors; Histone deacetylase; Homeostasis; in vitro; Inflammation; Intercellular adhesion molecule 1; Interleukin 1; Leukocytes; Metabolites; Neutrophils; Nuclear transport; Nuclei (cytology); oral biology; Oral cancer; Oral squamous cell carcinoma; Periodontium; Phosphorylation; Propionic acid; Squamous cell carcinoma; Trichostatin A; Tumor necrosis factor-α; epithelial cells; butyric acid; periodontium; oral biology; in vitro; intercellular adhesion molecule-1
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms21051679

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.