PARP9 and PARP14 cross-regulate macrophage activation via STAT1 ADP-ribosylation

Despite the global impact of macrophage activation in vascular disease, the underlying mechanisms remain obscure. Here we show, with global proteomic analysis of macrophage cell lines treated with either IFNγ or IL-4, that PARP9 and PARP14 regulate macrophage activation. In primary macrophages, PARP9 and PARP14 have opposing roles in macrophage activation. PARP14 silencing induces pro-inflammatory genes and STAT1 phosphorylation in M(IFNγ) cells, whereas it suppresses anti-inflammatory gene expression and STAT6 phosphorylation in M(IL-4) cells. PARP9 silencing suppresses pro-inflammatory genes and STAT1 phosphorylation in M(IFNγ) cells. PARP14 induces ADP-ribosylation of STAT1, which is suppressed by PARP9. Mutations at these ADP-ribosylation sites lead to increased phosphorylation. Network analysis links PARP9–PARP14 with human coronary artery disease. PARP14 deficiency in haematopoietic cells accelerates the development and inflammatory burden of acute and chronic arterial lesions in mice. These findings suggest that PARP9 and PARP14 cross-regulate macrophage activation

Artificial induction of third-stage dispersal juveniles of Bursaphelenchusxylophilus using newly established inbred lines

The pine wood nematode, Bursaphelenchus xylophilus, is the causal agent of pine wilt disease. This nematode has two developmental forms in its life cycle; i.e., the propagative and dispersal forms. The former is the form that builds up its population inside the host pine. The latter is specialized for transport by the vector. This form is separated into two dispersal stages (third and fourth); the third-stage dispersal juvenile (JIII) is specialized for survival under unfavorable conditions, whereas the fourth-stage juvenile (JIV), which is induced by a chemical signal from the carrier Monochamus beetle, is transported to new host pines and invades them. Because of its importance in the disease cycle, molecular and chemical aspects of the JIV have been investigated, while the mechanism of JIII induction has not been sufficiently investigated. In an effort to clarify the JIII induction process, we established inbred lines of B. xylophilus and compared their biological features. We found that the total number of nematodes (propagation proportion) was negatively correlated with the JIII emergence proportion, likely because nematode development was arrested at JIII; i.e., they could not develop to adults via the reproductive stage. In addition, JIII induction seemed to be regulated by a small number of genes because the JIII induction proportion varied among inbred lines despite the high homozygosity of the parental line. We also demonstrated that JIII can be artificially induced by the nematode’s secreted substances. This is the first report of artificial induction of JIII in B. xylophilus. The dauer (dispersal) juvenile of the model organism Caenorhabditis elegans corresponds functionally to JIII of B. xylophilus, and this stage is known to be induced by a chemical signal referred to as daumone, derived from the nematodes’ secretion. The artificial induction of JIII suggests the presence of daumone-like material in B. xylophilus