Untitled

Abstract

We studied the role of poly-ADP-ribose polymerase (PARP) in the mobilization of ICAM-1, VCAM-1, and E-selectin by TNF-alpha and IL-1beta in cultured human endothelial cells. Enzyme linked immunosorbent analysis (ELISA) was used to assess if ICAM-1, VCAM-1, and E-selectin were expressed at the cell surface, and if PARP inhibition (using the selective PARP inhibitor GPI 6150) blocked the induced expression. Endothelial cell adhesion molecule expression was evaluated at 4 and at 24 h after cytokine stimulation. At 4 h ICAM-1 and E-selectin, but not VACM-1, were stimulated by both IL-1beta and TNF-alpha. Blocking PARP via GPI 6150 only affected TNF-alpha induced E-selectin expression at 4 hours. ICAM-1, VCAM-1, and E-selectin expression were all stimulated by both IL-1beta and TNF-alpha in the 24 h assays. PARP inhibition with GPI 6150 blocked the IL-1beta mediated stimulation of both ICAM-1 and E-selectin expression, and blocked TNF-alpha stimulation of ICAM-1 expression at 24 h. These experiments suggest that specific PARP inhibition may provide a novel method of controlling leukocyte dependent inflammation through the reduction of ICAM-1 and E-selectin expression in endothelial cells in response to cytokines.

PARP-1 cleavage fragments: signatures of cell-death proteases in neurodegeneration

“…PARP-1 is also involved in modulating endothelial cell adhesion molecule expression (e.g. during atherogenesis) via its binding partner NF-κB [16,29,30]. PARP-1, 2 and 3 can activate CNS immune responses by promoting astrocyte production of inflammatory cytokines like TNF-α, IL-1β, nitric oxide and the chemokine CCL2 after challenge with Staphylococcus aureus , a common CNS infectious agent [14].…”

Oxidative stress and accelerated vascular aging: implications for cigarette smoking

“…Consistent with the stimulatory effect of CSE on NF-κB activation, the potent PARP inhibitor PJ34 (157) provided significant anti-inflammatory effects in CSE-treated coronary arterial endothelial cells (Figure 4). Drugs inhibiting PARP-1 activity also reduce NF-κB-dependent transcription of TNFα in glial cells (153) and prevent pro-inflammatory gene expression in cultured endothelial cells (158). In addition, both NF-κB activity and NF-κB -driven transcription of pro-inflammatory cytokines is markedly impaired in PARP-1 knockout animals (159, 160).…”

Poly(ADP‐Ribose)‐Polymerase‐Catalyzed Hydrolysis of NAD+: QM/MM Simulation of the Enzyme Reaction

“…PARP-1 is involved in a variety of processes related to the maintenance of genomic integrity, cell differentiation, and survival. Accordingly, PARP-1 is considered an attractive target for the development of therapeutic agents potentially useful in the treatment of pathological conditions such as brain [2] and heart [3] ischemia, inflammation, [4] and cancer. [5] Kinetic analysis, [6] mutational studies, [7,8] and crystallographic determinations [9][10][11][12] have permitted quite a clear elucidation of the catalytic potentiality of PARP-1.…”