Reduced Colonic Mucosal Injury in 2,3,7,8-Tetrachlorodibenzo-p-Dioxin Poly ADP-Ribose Polymerase (TIPARP/PARP7)-Deficient Mice

Abstract

Poly-ADP-ribose polymerases (PARPs) are important regulators of the immune system, including TCDD-inducible poly-ADP-ribose polymerase (TIPARP), also known as poly-ADP-ribose polymerase 7 (PARP7). PARP7 negatively regulates aryl hydrocarbon receptor (AHR) and type I interferon (IFN-I) signaling, both of which have been implicated in intestinal homeostasis and immunity. Since the loss of PARP7 expression increases AHR and IFN-I signaling, we used a murine dextran sulfate sodium (DSS)-induced colitis model to investigate the effect of PARP7 loss on DSS-induced intestinal inflammation. DSS-exposed Parp7−/− mice had less body weight loss, lower disease index scores, and reduced expression of several inflammation genes, including interleukin IL-6, C-x-c motif chemokine ligand 1 (Cxcl1), and lipocalin-2, when compared with wild-type mice. However, no significant difference was observed between genotypes in the colonic expression of the AHR target gene cytochrome P450 1A1 (Cyp1a1). Moreover, no significant differences in microbial composition were observed between the genotypes. Our findings demonstrate that the absence of PARP7 protein results in an impaired immune response to colonic inflammation and suggests that PARP7 may participate in the recruitment of immune cells to the inflammation site, which may be due to its role in IFN-I signaling rather than AHR signaling.

Polysaccharide from Atractylodes macrocephala Koidz Binding with Zinc Oxide Nanoparticles as a Novel Mucosal Immune Adjuvant for H9N2 Inactivated Vaccine

“…To reveal the species composition of the gut microbiota, the abundance of bacteria at different levels was evaluated. The number of Firmicutes was increased in the WIV + AMP-ZnONP group at the phylum level, possibly due to its ability to metabolize indigestible polysaccharides into short-chain fatty acids [39]. Compared with the control group, the WIV + CT and WIV + AMP-ZnONP groups exhibited contrasting trends in the abundance of Firmicutes and Bacteroidetes.…”

Are PARPs promiscuous?

“…PARP7 is one of the interferon-induced PARPs, which hints at a role for PARP7 in immunity [ 47 ]. In a colitis mouse model, Parp7 −/− mice displayed a milder phenotype, possibly by recruiting immune cells to the site of inflammation [ 77 ]. PARP7 was furthermore reported to MARylate TBK1, a major kinase activated during the type I interferon response, leading to inhibition of TBK1 and thereby suppressed interferon response [ 78 ].…”

Increased sensitivity to chemically induced colitis in mice harboring a DNA-binding deficient aryl hydrocarbon receptor

“…At the end of the experiment animals were euthanized, and liver, intestines, and colon were removed for gene expression, histological, and biochemical analyses. Feces were collected immediately before the start of the experiment and used to evaluate changes in the microbiome by a real-time qPCR-based method, as we and others have described (Hutin et al, 2022;Lamas et al, 2016;Yang et al, 2015). All animals were bred and cared for at the University of Toronto.…”

“…We next assessed the severity of inflammation using a daily disease activity index (DAI) assessment (Figure 4A) as described previously (Hutin et al, 2022;Kim et al, 2012). DSS exposed Ahr dbd/dbd mice displayed a significantly greater DAI than wild-type mice.…”