Dataset Information


Extracellular poly(ADP-ribose) is a pro-inflammatory signal for macrophages.

ABSTRACT: Poly(ADP-ribose) polymerase 1 (PARP1) synthesizes poly(ADP-ribose) (PAR), an essential post-translational modification whose function is important in many cellular processes including DNA damage signaling, cell death, and inflammation. All known PAR biology is intracellular, but we suspected it might also play a role in cell-to-cell communication during inflammation. We found that PAR activated cytokine release in human and mouse macrophages, a hallmark of innate immune activation, and determined structure-activity relationships. PAR was rapidly internalized by murine macrophages, while the monomer, ADP-ribose, was not. Inhibitors of Toll-like receptor 2 (TLR2) and TLR4 signaling blocked macrophage responses to PAR, and PAR induced TLR2 and TLR4 signaling in reporter cell lines suggesting it was recognized by these TLRs, much like bacterial pathogens. We propose that PAR acts as an extracellular damage associated molecular pattern that drives inflammatory signaling.

SUBMITTER: Krukenberg KA 

PROVIDER: S-EPMC4409933 | BioStudies | 2015-01-01

REPOSITORIES: biostudies

Similar Datasets

2012-01-01 | S-EPMC3306470 | BioStudies
2019-01-01 | S-EPMC6478412 | BioStudies
2013-01-01 | S-EPMC3759693 | BioStudies
2012-01-01 | S-EPMC3381899 | BioStudies
2016-01-01 | S-EPMC5026359 | BioStudies
1000-01-01 | S-EPMC1838747 | BioStudies
2020-01-01 | S-EPMC7442474 | BioStudies
2010-01-01 | S-EPMC2889080 | BioStudies
1000-01-01 | S-EPMC6089979 | BioStudies
2019-01-01 | S-EPMC6445106 | BioStudies