Tumor Necrosis Factor-Alpha Up-Regulates ICAM-1 Expression and Release in Intestinal Myofibroblasts by Redox-Dependent and -Independent Mechanisms

• Published in: Journal of cellular biochemistry 2016-02, Vol.117 (2), p.370-381
• Main Authors: Fontani, Filippo, Domazetovic, Vladana, Marcucci, Tommaso, Vincenzini, Maria Teresa, Iantomasi, Teresa
• Format: Article
• Language: English
• Subjects: ADAM Proteins - metabolism; ADAM17 Protein; Cell Line; H2O2 PRODUCTION; Humans; ICAM-1 SOLUBLE FORM; Intercellular Adhesion Molecule-1 - genetics; Intercellular Adhesion Molecule-1 - metabolism; Intestines - cytology; Intestines - metabolism; Matrix Metalloproteinases - metabolism; Myofibroblasts - metabolism; Myofibroblasts - secretion; NADPH Oxidases - metabolism; Oxidation-Reduction; OXIDATIVE STRESS; Phosphorylation; Reactive Oxygen Species - metabolism; REDOX REGULATION; TACE; Transcriptional Activation; Tumor Necrosis Factor-alpha - physiology; Up-Regulation
• ISSN: 0730-2312; 1097-4644
• DOI: 10.1002/jcb.25279

ABSTRACT Intercellular adhesion molecule‐1 (ICAM‐1) is distributed and expressed on cell surface and is present in circulation as soluble form (sICAM‐1). Tumor necrosis factor‐alpha (TNFα) and radical oxygen species (ROS) up‐regulate the expression of ICAM‐1. This study demonstrates for the first time in 18 Co cells, a myofibroblast cell line derived from human colonic mucosa, an up‐regulation of ICAM‐1 expression and sICAM‐1 release induced by oxidative stress and TNFα stimulation. The intracellular redox state was modulated by L‐buthionine‐S,R‐sulfoximine (BSO) or N‐acetylcysteine (NAC), inhibitor and precursor respectively of GSH synthesis. ROS production increases in cells treated with BSO or TNFα, and this has been related to an up‐regulation of ICAM‐1 expression and sICAM‐1 release. The involvement of metalloproteinases in ICAM‐1 release has been demonstrated. Moreover, also expression and activation of A disintegrin and metalloproteinase 17, a membrane‐bound enzyme known as TNFα‐converting enzyme (TACE), have been related to ROS levels. This suggests the possible involvement of TACE in the cleavage of ICAM‐1 on cell surface in condition of oxidative stress. NAC down‐regulates the expression and release of ICAM‐1 as well as the expression and activation of TACE. However, in TNFα stimulated cells NAC treatment reduces only in part ICAM‐1 expression and sICAM‐1 release. Given this TNFα may also act on these events by a redox‐independent mechanism. J. Cell. Biochem. 117: 370–381, 2016. © 2015 Wiley Periodicals, Inc.