Centaurin β1 Down-regulates Nucleotide-binding Oligomerization Domains 1- and 2-dependent NF-κB Activation

Yan²,

Proc. Natl. Acad. Sci. U.S.A.

et al. 2010

126

151

Olfactomedin 4 (OLFM4) is a glycoprotein that has been found to be up-regulated in inflammatory bowel diseases and Helicobacter pylori infected patients. However, its role in biological processes such as inflammation or other immune response is not known. In this study, we generated OLFM4 KO mice to investigate potential role(s) of OLFM4 in gastric mucosal responses to H. pylori infection. H. pylori colonization in the gastric mucosa of OLFM4 KO mice was significantly lower compared with WT littermates. The reduced bacterial load was associated with enhanced infiltration of inflammatory cells in gastric mucosa. Production and expression of proinflammatory cytokines/chemokines such as IL-1β, IL-5, IL-12 p70, and MIP-1α was increased in OLFM4 KO mice compared with infected controls. Furthermore, we found that OLFM4 is a target gene of NF-κB pathway and has a negative feedback effect on NF-κB activation induced by H. pylori infection through a direct association with nucleotide oligomerization domain-1 (NOD1) and -2 (NOD2). Together these observations indicate that OLFM4 exerts considerable influence on the host defense against H. pylori infection acting through NOD1 and NOD2 mediated NF-κB activation and subsequent cytokines and chemokines production, which in turn inhibit host immune response and contribute to persistence of H. pylori colonization.NF-κB | nucleotide oligomerization domain-1 and -2

Section: Discussionmentioning

confidence: 99%

Olfactomedin 4 down-regulates innate immunity against Helicobacter pylori infection

Yan²,

Proc. Natl. Acad. Sci. U.S.A.

et al. 2010

126

151

Biochemical Pharmacology

“…The cell polarity protein Erbin, the GTPase-activating protein Centaurin-b1 (CENTB1) and the angioassociated migratory cell protein (AAMP) bind to Nod2 and negatively regulate Nod2-dependent NF-kB activation while the GRIM-19 protein that also associates with Nod2 appears to positively modulate Nod2 signalling [25,26,[45][46][47]. Since Erbin and CENTB1 expression is upregulated after Nod2 activation, both proteins could mediate a negative feedback.…”

Section: A Lecat Et Al / Biochemical Pharmacology XXX (2010) Xxx-xxxmentioning

confidence: 99%

The protein Nod2: An innate receptor more complex than previously assumed

Lecat

Piette

Legrand-Poels

2010

Please check your proof carefully and mark all corrections at the appropriate place in the proof (e.g., by using on-screen annotation in the PDF file) or compile them in a separate list.For correction or revision of any artwork, please consult http://www.elsevier.com/artworkinstructions.Any queries or remarks that have arisen during the processing of your manuscript are listed below and highlighted by flags in the proof. Click on the 'Q' link to go to the location in the proof. Location inQuery / Remark: click on the Q link to go article Please insert your reply or correction at the corresponding line in the proof Q1If there are fewer than seven authors, please supply all their names; if there are seven or more authors, please supply the first six authors' names, followed by 'et al.'Thank you for your assistance. Graphical AbstractBiochemical Pharmacology xxx (2010) xxx-xxx pp: xxx-xxx The protein Nod2: An innate receptor more complex than previously assumed

“…Through the recognition of MDP, secretion of alpha-defensins is stimulated for protection against microbial invasion. In CD patients, a diminished expression of alpha-defensins has been found in those carriers with NOD2 mutation [20,21] . It is known that through this recognition of bacterial products the nuclear factor kappa B (NFκB) activation is regulated [10,22] .…”

Section: Ibd1mentioning

confidence: 99%

Novel genetic markers in inflammatory bowel disease

Rodríguez-Bores

Fonseca²,

Villeda³

et al. 2007

WJG

Genetic factors play a significant role in determining inflammatory bowel disease (IBD) susceptibility. Epidemiologic data support genetic contribution to the pathogenesis of IBD, which include familial aggregation, twin studies, racial and ethnic differences in disease prevalence. Linkage studies have identified several susceptibility genes contained in different genomic regions named IBD1 to IBD9. Nucleotide oligomerization domain (NOD2) and human leukocyte antigen (HLA) genes are the most extensively studied genetic regions (IBD1 and IBD3 respectively) in IBD. Mutations of the NOD2 gene are associated with Crohn's disease (CD) and several HLA genes are associated with ulcerative colitis (UC) and CD. Toll like receptors (TLRs) have an important role in the innate immune response against infections by mediating recognition of pathogen-associated microbial patterns. Studying single-nucleotide polymorphisms (SNPs) in molecules involved in bacterial recognition seems to be essential to define genetic backgrounds at risk of IBD. Recently, numerous new genes have been identified to be involved in the genetic susceptibility to IBD: NOD1/Caspase-activation recruitment domains 4 (CARD4), Chemokine ligand 20 (CCL20), IL-11, and IL-18 among others. The characterization of these novel genes potentially will lead to the identification of therapeutic agents and clinical assessment of phenotype and prognosis in patients with IBD.