Pro-Inflammatory Stimuli Influence Expression of Intercellular Adhesion Molecule 1 in Human Anulus Fibrosus Cells through FAK/ERK/GSK3 and PKCδ Signaling Pathways.

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.

EGFR is a pivotal regulator of thrombin-mediated inflammation in primary human nucleus pulposus culture.

We found that the coagulation and cytokine pathways were important mechanisms involve in the degeneration of intervertebral discs (IVD) using a microarray approach to analyze gene expression in different grades of specimens. Furthermore, using a cytokine/chemokine array, a significant increase in CXCL8 expression was observed in human nucleus pulposus (NP) cells after thrombin treatment. The enhancement of CXCL8 expression by thrombin was activated by the PAR1 receptor.

The anti-angiogenic action of 2-deoxyglucose involves attenuation of VEGFR2 signaling and MMP-2 expression in HUVECs.

Aims: 2-Deoxyglucose (2-DG) is a glucose analogue and has been shown to inhibit angiogenesis in human umbilical vascular endothelial cells (HUVECs) through interference with N-linked glycosylation. However, the anti-angiogenic mechanisms of 2-DG are not fully elucidated.

Main Methods: We first employed an ex vivo rat aortic ring model to substantiate the anti-angiogenic action of 2-DG and then used HUVECs to investigate the molecular mechanism underlying such an action.