Nucleotide-binding oligomerization domain 1(NOD1) is an intracellular innate immune sensor for small molecules derived from bacterial cell components. NOD1 activation by its ligands leads to robust production of pro-i...Nucleotide-binding oligomerization domain 1(NOD1) is an intracellular innate immune sensor for small molecules derived from bacterial cell components. NOD1 activation by its ligands leads to robust production of pro-inflammatory cytokines and chemokines by innate immune cells, thereby mediating mucosal host defense systems against microbes. Chronic gastric infection due to Helicobacter pylori(H. pylori) causes various upper gastrointestinal diseases, including atrophic gastritis, peptic ulcers, and gastric cancer. It is now generally accepted that detection of H. pylori by NOD1 expressed in gastric epithelial cells plays an indispensable role in mucosal host defense systems against this organism. Recent studies have revealed the molecular mechanism by which NOD1 activation caused by H. pylori infection is involved in the development of chronic gastritis and gastric cancer. In this review, we have discussed and summarized how sensing of H. pylori by NOD1 mediates the prevention of chronic gastritis and gastric cancer.展开更多
Objective To investigate the potential role of nucleotide-binding oligomerization domain 1(NOD1),a component of the innate immune system,in mediating lipid-induced insulin resistance in adipocytes.Methods Adipocytes f...Objective To investigate the potential role of nucleotide-binding oligomerization domain 1(NOD1),a component of the innate immune system,in mediating lipid-induced insulin resistance in adipocytes.Methods Adipocytes from Toll-like receptor 4 deficiency mice were used for stimulation experiments.The effect of oleate/palmitate mixture on nuclear factor-κB(NF-κB)activation was analyzed by reporter plasmid assay.The release of proinflammatory chemokine/cytokines production was determined by using real-time PCR.Insulin-stimulated glucose uptake was measured by 2-deoxy-D-[3H]glucose uptake assay.Chemokine/cytokine expression and glucose uptake in adipocytes transfected with small interfering RNA(siRNA)targeting NOD1 upon fatty acids treatment were analyzed.Results Oleate/palmitate mixture activated the NF-κB pathway and induced interleukin-6,tumor necrosis factor-α,and monocyte chemoattractant protein-1 mRNA expressions in adipocytes from mice deficient in Toll-like receptor 4,and these effects were blocked by siRNA targeting NOD1.Furthermore,saturated fatty acids decreased the ability of insulin-stimulated glucose uptake.Importantly,siRNA targeting NOD1 partially reversed saturated fatty acid-induced suppression of insulin-induced glucose uptake.Conclusion NOD1 might play an important role in saturated fatty acid-induced insulin resistance in adipocytes,suggesting a mechanism by which reduced NOD1 activity confers beneficial effects on insulin action.展开更多
Objective To investigate the effects of stimulant for nucleotide-binding oligomerization domain 1 (NOD1) on secretion of proinflammatory chemokine/cytokines and insulin-dependent glucose uptake in human differentiated...Objective To investigate the effects of stimulant for nucleotide-binding oligomerization domain 1 (NOD1) on secretion of proinflammatory chemokine/cytokines and insulin-dependent glucose uptake in human differentiated adipocytes. Methods Adipose tissues were obtained from patients undergoing liposuction. Stromal vascular cells were extracted and differentiated into adipocytes. A specific ligand for NOD1, was administered to human adipocytes in culture. Nuclear factor-κB transcriptional activity and proinflammatory chemokine/cytokines production were determined by reporter plasmid assay and enzyme-linked immunosorbent assay, respectively. Insulin-stimulated glucose uptake was measured by 2-deoxy-D-[ 3 H] glucose uptake assay. Furthermore, chemokine/cytokine secretion and glucose uptake in adipocytes transfected with small interfering RNA (siRNA) targeting NOD1展开更多
AIM: To examine genetic variation of nucleotide oligomerization domain 1 (NOD1 ) and NOD2 ,their respective influences on Crohn's disease phenotype and gene-gene interactions. METHODS: (ND1+326561 ) NOD1 polymorph...AIM: To examine genetic variation of nucleotide oligomerization domain 1 (NOD1 ) and NOD2 ,their respective influences on Crohn's disease phenotype and gene-gene interactions. METHODS: (ND1+326561 ) NOD1 polymorphism and SNP8,SNP12 and SNP13 of NOD2 were analyzed in 97 patients and 50 controls. NOD2 variants were determined by reaction restriction fragment length polymorphism analysis. NOD1 genotyping and NOD2 variant confirmation were performed by specific amplification and sequencing. RESULTS: The distribution of NOD1 polymorphism in patients was different from controls (P = 0.045) and not altered by existence of NOD2 mutations. In this cohort,30.92% patients and 6% controls carried at least one NOD2 variant (P < 0.001) with R702W being the most frequent variant. Presence of at least one NOD2 mutation was inversely associated with colon involvement (9.09% with colon vs 36.4% with ileal or ileocolonic involvement,P = 0.04) and indicative of risk of penetrating disease (52.63% with penetrating vs 25.64% with non-penetrating or stricturing behavior,P = 0.02). L1007finsC and double NOD2 mutation conferred the highest risk for severity of disease (26.3% with penetrating disease vs 3.8% with non-penetrating or stricturing behavior presented L1007finsC,P = 0.01 and 21.0% with penetrating disease vs 2.5% with non-penentrating or stricturing behavior carried double NOD2 mutation,P = 0.007). Exclusion of patients with NOD2 mutations from phenotype/NOD1 -genotype analysis revealed higher prevalence of 11 genotype in groups of younger age at onset and colonic location. CONCLUSION: This study suggests population differences in the inheritance of risk NOD1 polymorphism and NOD2 mutations. Although no interaction between NOD1 -NOD2 was noticed,a relationship between disease location and Nod-like receptor molecules was established.展开更多
文摘Nucleotide-binding oligomerization domain 1(NOD1) is an intracellular innate immune sensor for small molecules derived from bacterial cell components. NOD1 activation by its ligands leads to robust production of pro-inflammatory cytokines and chemokines by innate immune cells, thereby mediating mucosal host defense systems against microbes. Chronic gastric infection due to Helicobacter pylori(H. pylori) causes various upper gastrointestinal diseases, including atrophic gastritis, peptic ulcers, and gastric cancer. It is now generally accepted that detection of H. pylori by NOD1 expressed in gastric epithelial cells plays an indispensable role in mucosal host defense systems against this organism. Recent studies have revealed the molecular mechanism by which NOD1 activation caused by H. pylori infection is involved in the development of chronic gastritis and gastric cancer. In this review, we have discussed and summarized how sensing of H. pylori by NOD1 mediates the prevention of chronic gastritis and gastric cancer.
基金Supported by the Grant from the Educational Department of Liaoning Province(2008810)
文摘Objective To investigate the potential role of nucleotide-binding oligomerization domain 1(NOD1),a component of the innate immune system,in mediating lipid-induced insulin resistance in adipocytes.Methods Adipocytes from Toll-like receptor 4 deficiency mice were used for stimulation experiments.The effect of oleate/palmitate mixture on nuclear factor-κB(NF-κB)activation was analyzed by reporter plasmid assay.The release of proinflammatory chemokine/cytokines production was determined by using real-time PCR.Insulin-stimulated glucose uptake was measured by 2-deoxy-D-[3H]glucose uptake assay.Chemokine/cytokine expression and glucose uptake in adipocytes transfected with small interfering RNA(siRNA)targeting NOD1 upon fatty acids treatment were analyzed.Results Oleate/palmitate mixture activated the NF-κB pathway and induced interleukin-6,tumor necrosis factor-α,and monocyte chemoattractant protein-1 mRNA expressions in adipocytes from mice deficient in Toll-like receptor 4,and these effects were blocked by siRNA targeting NOD1.Furthermore,saturated fatty acids decreased the ability of insulin-stimulated glucose uptake.Importantly,siRNA targeting NOD1 partially reversed saturated fatty acid-induced suppression of insulin-induced glucose uptake.Conclusion NOD1 might play an important role in saturated fatty acid-induced insulin resistance in adipocytes,suggesting a mechanism by which reduced NOD1 activity confers beneficial effects on insulin action.
基金Supported by Grant from Department of Education of Liaoning Province(2008810)
文摘Objective To investigate the effects of stimulant for nucleotide-binding oligomerization domain 1 (NOD1) on secretion of proinflammatory chemokine/cytokines and insulin-dependent glucose uptake in human differentiated adipocytes. Methods Adipose tissues were obtained from patients undergoing liposuction. Stromal vascular cells were extracted and differentiated into adipocytes. A specific ligand for NOD1, was administered to human adipocytes in culture. Nuclear factor-κB transcriptional activity and proinflammatory chemokine/cytokines production were determined by reporter plasmid assay and enzyme-linked immunosorbent assay, respectively. Insulin-stimulated glucose uptake was measured by 2-deoxy-D-[ 3 H] glucose uptake assay. Furthermore, chemokine/cytokine secretion and glucose uptake in adipocytes transfected with small interfering RNA (siRNA) targeting NOD1
基金Supported by a grant of Ministerio Educacion y Ciencia (BFU 2006-15063)E.C.is participant of the Program "Contratos de apoyo a la Investigacion del Sistema Nacional de Salud". S.V. was supported by "Fondo Investigaciones Sanitarias" and participant of the Program for Stabilization of Investigators of "Direccio d’ Estrategia i Coordinacio del Departament Salut de la Generalitat de Catalunya"
文摘AIM: To examine genetic variation of nucleotide oligomerization domain 1 (NOD1 ) and NOD2 ,their respective influences on Crohn's disease phenotype and gene-gene interactions. METHODS: (ND1+326561 ) NOD1 polymorphism and SNP8,SNP12 and SNP13 of NOD2 were analyzed in 97 patients and 50 controls. NOD2 variants were determined by reaction restriction fragment length polymorphism analysis. NOD1 genotyping and NOD2 variant confirmation were performed by specific amplification and sequencing. RESULTS: The distribution of NOD1 polymorphism in patients was different from controls (P = 0.045) and not altered by existence of NOD2 mutations. In this cohort,30.92% patients and 6% controls carried at least one NOD2 variant (P < 0.001) with R702W being the most frequent variant. Presence of at least one NOD2 mutation was inversely associated with colon involvement (9.09% with colon vs 36.4% with ileal or ileocolonic involvement,P = 0.04) and indicative of risk of penetrating disease (52.63% with penetrating vs 25.64% with non-penetrating or stricturing behavior,P = 0.02). L1007finsC and double NOD2 mutation conferred the highest risk for severity of disease (26.3% with penetrating disease vs 3.8% with non-penetrating or stricturing behavior presented L1007finsC,P = 0.01 and 21.0% with penetrating disease vs 2.5% with non-penentrating or stricturing behavior carried double NOD2 mutation,P = 0.007). Exclusion of patients with NOD2 mutations from phenotype/NOD1 -genotype analysis revealed higher prevalence of 11 genotype in groups of younger age at onset and colonic location. CONCLUSION: This study suggests population differences in the inheritance of risk NOD1 polymorphism and NOD2 mutations. Although no interaction between NOD1 -NOD2 was noticed,a relationship between disease location and Nod-like receptor molecules was established.
