Chemical and cytokine features of innate immunity characterize serum and tissue profiles in inflammatory bowel disease

Abstract

Significance Our study investigates chemical damage associated with chronic inflammation and relates these macromolecular damage products to inflammatory bowel disease activity. Using mice as a model system, we show that chronic inflammatory responses that are common to mice and humans produce similar types and quantities of damage products in both species. Additional analysis of signaling molecules in the serum and tissue of diseased samples highlights the role of the innate immune response in the overall pathology of inflammatory bowel disease.

Isolation and characterization of a novel Helicobacter species, Helicobacter jaachi sp. nov., from common marmosets (Callithrix jaachus)

“…Further, numerous experimental Helicobacter sp. infections in mice have reproduced salient features of IBD and hepatobiliary disease observed in marmosets (Erdman et al, 2009;Fox, 2002;Fox et al, 1996Fox et al, , 2011Hailey et al, 1998;Knutson et al, 2013;Maggio-Price et al, 2005;Mangerich et al, 2012;Meeker et al, 2014).…”

“…Helicobacter species that colonize the lower bowel and biliary tract of non-human primates have been routinely isolated from cases with chronic inflammation of the lower bowel (Fox et al, 2001a(Fox et al, , b, 2007Lertpiriyapong et al, 2014;Marini et al, 2010;Saunders et al, 1999;Won et al, 2007). The importance of these findings is augmented by experimental studies in mice which demonstrate that H. hepaticus, the prototype enterohepatic Helicobacter species (EHS), has been shown to play a central role in the development of chronic inflammation and cancer at both intestinal and extraintestinal sites, in both immunocompromised and immunosuppressed mice (Erdman et al, 2009;Fox et al, 1996Fox et al, , 2011García et al, 2011;Knutson et al, 2013).…”

NovelHelicobacterspeciesH.japonicumisolated from laboratory mice from Japan induces typhlocolitis and lower bowel carcinoma in C57BL/129 IL10−/−mice

“…CDT has nuclease activity, causes DNA DSBs, inhibits ATM-dependent response pathways and suppresses repair of DNA adducts. Importantly, H.hepaticus infection in 129 rag deficient mice cause inflammatory immune responses associated with highly reactive oxygen and nitrogen species capable of causing tissue injury, death or mutation of cells (49)(50)(51). Further, DSBs have been involved with H.pylori-induced gastric cancer (52).…”

Intrinsic mutagenic properties of 5-chlorocytosine: A mechanistic connection between chronic inflammation and cancer

“…In one study, the levels of 5ClC in both DNA and RNA were elevated in the colon of Rag2 −/− mice infected with Helicobacter hepaticus, a model of chronic inflammation in the gut (20). In a follow-up study, the same biomarkers were found at similarly high levels in colonic tissue samples from human patients with inflammatory bowel disease (Crohn's disease or ulcerative colitis) (21). Surprisingly, these studies did not find significantly increased levels of classical DNA biomarkers of inflammation and oxidative stress, such as 8-oxo-7,8-dihydroguanine (8oxoG) and other oxidative DNA lesions (20,21).…”

“…The main biomarkers found in cells exposed to HOCl are chlorinated tyrosines (in proteins) and chlorinated nucleobases (in nucleic acids and nucleotide pools) (15,16). Among the chlorinated nucleobases, 5-chlorocytosine (5ClC) is the most abundant (16)(17)(18)(19) and recently has been recognized as a biomarker associated with chronic inflammation (20,21). In one study, the levels of 5ClC in both DNA and RNA were elevated in the colon of Rag2 −/− mice infected with Helicobacter hepaticus, a model of chronic inflammation in the gut (20).…”