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

Gabriel Leonardo Magrin,Reinhard Gruber,Layla Panahipour,Cesar Augusto Magalhães Benfatti,Franz-Josef Strauss,Michael Mildner,Francesca Di Summa

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.

Highlights

Oral health requires the cellular immunity of the oral mucosal barrier that extends towards the periodontium to defend the tooth-bearing tissue against commensal microbes and other antigens of the oral cavity [1]
The junctional epithelium controls the transmigration of neutrophils towards the crevicular fluid by means of a tightly controlled expression of adhesion molecules, thereby defending microbiological antagonism in the periodontal tissue [2,3]
The influx of cells is controlled by intercellular adhesion molecule-1 (ICAM-1), allowing the transmigration of leucocytes which express the corresponding lymphocyte function-associated antigen-1 and macrophage adhesion ligand-1 [4]

Summary

Introduction

Oral health requires the cellular immunity of the oral mucosal barrier that extends towards the periodontium to defend the tooth-bearing tissue against commensal microbes and other antigens of the oral cavity [1]. The junctional epithelium controls the transmigration of neutrophils towards the crevicular fluid by means of a tightly controlled expression of adhesion molecules, thereby defending microbiological antagonism in the periodontal tissue [2,3]. The increase of adhesion molecules by inflammatory mediators has to be counterbalanced by local cues to control an excessive influx of cells of the innate immune system. The influx of cells is controlled by intercellular adhesion molecule-1 (ICAM-1), allowing the transmigration of leucocytes which express the corresponding lymphocyte function-associated antigen-1 and macrophage adhesion ligand-1 [4]. ICAM-1, being induced by inflammatory cues such as interleukin-1-beta (IL1β) and tumor necrosis factor-α (TNFα) [5], is expressed by the vascular endothelium and by the junctional epithelium [6], facilitating transmigration of leukocytes across vascular endothelia and the invasion of the extracellular matrix [7]. The question arises, how is the expression of ICAM-1 in epithelial cells controlled?

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Methods

Results