Low shear stress induced HMGB1 translocation and release via PECAM-1/PARP-1 pathway to induce inflammation response.

Abstract

Low shear stress (LSS) plays a critical role in the site predilection of atherosclerosis through activation of cellular mechanosensors, such as platelet endothelial cell adhesion molecule 1 (PECAM-1). Poly(ADP-ribose) polymerase 1 (PARP-1) is a nuclear enzyme that regulates the expression of various inflammatory cytokines. The nuclear enzyme high mobility group box 1 (HMGB1) can induce inflammation response by binding to toll-like receptor 4 (TLR4). In the present study, we aimed to investigate the role and mechanism of HMGB1 in LSS induced inflammation in human umbilical vein endothelial cells (HUVECs). HUVECs were stimulated by undisturbed shear stress (USS, 1 Pa) and LSS (0.4 Pa) in our experiments. Gene expression was inhibited by small interfering RNA (siRNA). ICAM-1 expression was regulated by LSS in a time dependent manner. LSS can induce HMGB1 translocation from nucleus to cytoplasm and release. Compared with the USS, LSS could increase the protein expression of PECAM-1 and PARP-1 as well as the secretion of TNF-α and IL-1β. LSS induced the translocation of HMGB1 from nucleus to cytoplasm. Inhibition of HGMB1 reduced LSS-induced inflammatory response. Inhibition of PARP-1 suppressed inflammatory response through inhibiting TLR4 expression and HMGB1 translocation. PECAM-1 inhibition reduced LSS-induced ICAM-1 expression, TNF-α and IL-1β secretion, and monocytes adhesion. LSS can induce inflammatory response via PECAM-1/PARP-1/HMGB1 pathway. PARP-1 plays a fundamental role in HMGB1 translocation and TLR4 expression. Inhibition of PARP-1 may shed light on the treatment of HMGB1 involved inflammation during atherosclerosis.

• Authors: Wei-dong Qin, Shao-hua Mi, Chen Li, Gui-xia Wang, Jian-ning Zhang, Hao Wang, Fan Zhang, Yang Ma, Da-wei Wu, Mingxiang Zhang
• Journal: PloS one (PLoS One) Vol. 10 Issue 3 Pg. e0120586 ( 2015) ISSN: 1932-6203 [Electronic] United States
• PMID: 25793984 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• HMGB1 Protein
• Interleukin-1beta
• Platelet Endothelial Cell Adhesion Molecule-1
• Toll-Like Receptor 4
• Tumor Necrosis Factor-alpha
• Intercellular Adhesion Molecule-1
• Poly(ADP-ribose) Polymerases

Topics

• HMGB1 Protein (antagonists & inhibitors, metabolism)
• Human Umbilical Vein Endothelial Cells (metabolism)
• Humans
• Inflammation (metabolism, pathology)
• Intercellular Adhesion Molecule-1 (metabolism)
• Interleukin-1beta (metabolism)
• Platelet Endothelial Cell Adhesion Molecule-1 (metabolism)
• Poly(ADP-ribose) Polymerases (metabolism)
• Protein Transport
• Shear Strength
• Signal Transduction
• Stress, Mechanical
• Time Factors
• Toll-Like Receptor 4 (metabolism)
• Tumor Necrosis Factor-alpha (metabolism)
• Up-Regulation