title: Nod1 acts as an intracellular receptor to stimulate chemokine production and neutrophil recruitment in vivo.
abstract: Nod1 is a member of family of intracellular proteins that mediate host recognition of bacterial peptidoglycan. To characterize immune responses mediated by Nod1, synthetic ligand compounds possessing enhanced ability to stimulate Nod1 were developed to study the function of Nod1. Stimulation of epithelial cells with Nod1 stimulatory molecules induced chemokines and other proinflammatory molecules that are important for innate immune responses and recruitment of acute inflammatory cells. Administration of Nod1 ligands into mice induced chemokines and recruitment of acute inflammatory cells, an activity that was abolished in Nod1-null mice. Microarray analysis revealed that Nod1 stimulation induces a restricted number of genes in intestinal epithelial cells compared with that induced by tumor necrosis factor (TNF) alpha. Nod1 stimulation did not induce TNFalpha, interleukin 12, and interferon gamma, suggesting that the primary role of Nod1 is to induce the recruitment of immune cells. These results indicate that Nod1 functions as a pathogen recognition molecule to induce expression of molecules involved in the early stages of the innate immune response.
authors.affiliation: Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
authors.forename: Junya
authors.initials: J
authors.lastname: Masumoto
authors.forename: Kangkang
authors.initials: K
authors.lastname: Yang
authors.forename: Sooryanarayana
authors.initials: S
authors.lastname: Varambally
authors.forename: Mizuho
authors.initials: M
authors.lastname: Hasegawa
authors.forename: Scott A
authors.initials: SA
authors.lastname: Tomlins
authors.forename: Su
authors.initials: S
authors.lastname: Qiu
authors.forename: Yukari
authors.initials: Y
authors.lastname: Fujimoto
authors.forename: Akiko
authors.initials: A
authors.lastname: Kawasaki
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Foster
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Horie
authors.forename: Tak W
authors.initials: TW
authors.lastname: Mak
authors.forename: Gabriel
authors.initials: G
authors.lastname: Núñez
authors.forename: Arul M
authors.initials: AM
authors.lastname: Chinnaiyan
authors.forename: Koichi
authors.initials: K
authors.lastname: Fukase
authors.forename: Naohiro
authors.initials: N
authors.lastname: Inohara
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D000818:Animals; D001426:Bacterial Proteins / Q000276:immunology; D002460:Cell Line; D016207:Cytokines / Q000276:immunology*; D004151:Dipeptides / Q000276:immunology; D004847:Epithelial Cells / Q000276:immunology; D006801:Humans; D007413:Intestinal Mucosa / Q000276:immunology; D008024:Ligands; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009504:Neutrophils / Q000276:immunology*; D053474:Nod1 Signaling Adaptor Protein; D020411:Oligonucleotide Array Sequence Analysis
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D001426:Bacterial Proteins; D016207:Cytokines; D004151:Dipeptides; D008024:Ligands; D053474:Nod1 Signaling Adaptor Protein; C507873:Nod1 protein, mouse