Pro-Inflammatory Stimuli Influence Expression of Intercellular Adhesion Molecule 1 in Human Anulus Fibrosus Cells through FAK/ERK/GSK3 and PKCδ Signaling Pathways
In: International Journal of Molecular Sciences, Jg. 20 (2018-12-01), Heft 1
Online
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Zugriff:
Objective: Intervertebral disc (IVD) degeneration and disc herniation are major causes of lower back pain, which involve the presence of inflammatory mediators and tissue invasion by immune cells. Intercellular adhesion molecule 1 (ICAM1, also termed CD54) is an adhesion molecule that mediates cell-cell interactions, particularly between immune cells and target tissue. The aim of this study was to examine the intracellular signaling pathways involved in inflammatory stimuli-induced ICAM1 expression in human anulus fibrosus (AF) cells. Methods: Quantitative reverse transcription-polymerase chain reaction (qPCR), western blotting, and flow cytometry were performed to dissect the roles of different signaling pathways in inflammatory stimuli-mediated ICAM1 expression. Results: Using qPCR and western blot analyses, a significant increase in ICAM1 expression was observed in AF cells after stimulation of lipopolysaccharide (LPS) plus interferon-gamma (IFN&gamma
) in a time-dependent manner. Flow cytometry revealed ICAM1 upregulation on the surface of AF cells. Importantly, LPS plus IFN&gamma
treatment also significantly promoted Chemokine ligand (CCL)2 expression, but not CCL3. The enhanced ICAM1 expression was abolished after incubation with antibody against CCL2. In AF cells, treatment with LPS plus IFN&gamma
activated the FAK/ERK/GSK3 signaling pathways, promoted a time-dependent increase in PKC&delta
phosphorylation, and promoted PKC&delta
translocation to the nucleus. Treatment with the pharmacological PKC&delta
inhibitor
rottlerin, effectively blocked the enhanced productions of ICAM1 and CCL2. Conclusions: Inflammatory stimuli in AF cells are part of a specific pathophysiology in IVD degeneration and disc herniation that modulates CCL2/ICAM1 activation through the FAK/ERK/GSK3 and PKC&delta
signaling pathways in AF cells.
Titel: |
Pro-Inflammatory Stimuli Influence Expression of Intercellular Adhesion Molecule 1 in Human Anulus Fibrosus Cells through FAK/ERK/GSK3 and PKCδ Signaling Pathways
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Autor/in / Beteiligte Person: | Tsai, Cheng-Fang ; Chuang, I-Chen ; Lu, Dah-Yuu ; Chang, Pei-Chun ; Da Tian Bau ; Huang, Bor-Ren ; Hsu, Horng-Chaung ; Chen, Tzu-Sheng |
Link: | |
Zeitschrift: | International Journal of Molecular Sciences, Jg. 20 (2018-12-01), Heft 1 |
Veröffentlichung: | MDPI AG, 2018 |
Medientyp: | unknown |
ISSN: | 1422-0067 (print) |
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