PARPs and ADP-Ribosylation in Chronic Inflammation: A Focus on Macrophages

Abstract

Aberrant adenosine diphosphate-ribose (ADP)-ribosylation of proteins and nucleic acids is associated with multiple disease processes such as infections and chronic inflammatory diseases. The poly(ADP-ribose) polymerase (PARP)/ADP-ribosyltransferase (ART) family members promote mono- or poly-ADP-ribosylation. Although evidence has linked PARPs/ARTs and macrophages in the context of chronic inflammation, the underlying mechanisms remain incompletely understood. This review provides an overview of literature focusing on the roles of PARP1/ARTD1, PARP7/ARTD14, PARP9/ARTD9, and PARP14/ARTD8 in macrophages. PARPs/ARTs regulate changes in macrophages during chronic inflammatory processes not only via catalytic modifications but also via non-catalytic mechanisms. Untangling complex mechanisms, by which PARPs/ARTs modulate macrophage phenotype, and providing molecular bases for the development of new therapeutics require the development and implementation of innovative technologies.

PAR level mediates the link between ROS and inflammatory response in patients with type 2 diabetes mellitus

“…Inflammation is a tissue response to stress caused by hyperglycemia, and PARylation is an important mediator in the inflammatory response [ 29 , 53 , 54 ]. It has been proposed that long-term, low-level chronic inflammation associated with the onset and/or worsening of several diseases, including diabetes, is largely dependent on PARylation, as demonstrated in various experimental models based on PARP enzyme inhibition or genetic deletion [ [54] , [55] , [56] ]. In line with these observations, studies on T2DM patients indicate that molecules that can counteract PARP enzymes activation show efficacy in attenuating cytokine release by blood cells [ 57 ] and in improving skin vascular function [ 58 ].…”