Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 9 de 9
Filter
Add more filters










Database
Language
Publication year range
1.
Stem Cells Dev ; 32(1-2): 32-43, 2023 01.
Article in English | MEDLINE | ID: mdl-36453206

ABSTRACT

Increasing adipogenesis has been explored to treat metabolic diseases and atherosclerosis through the release of adiponectin. The effects and mechanism of platelet-rich plasma treatment on fat graft survival and adipogenesis have not been clarified. Here, we aimed to study the effects of monocyte chemoattractant protein-1 (MCP-1)-supplemented plasma on adipogenesis-related gene expression and adiponectin levels. Stromal vascular fractions (SVFs) purified from the inguinal adipose tissue of obese and diabetic (Leprdb/db) mice were treated with plasma from control (Lepr+/+) mice supplemented with 10 or 50 ng of MCP-1. The expression of adiponectin and interleukin-33 (IL-33) mRNA in adipose tissue was increased in Leprdb/db mice, whereas control (Lepr+/+) plasma reduced expression of IL-33 mRNA as well as peroxisome proliferator-activated receptor gamma (PPARγ), pJNK, and pNF-κB protein, and increased the expression of IL-10 mRNA in SVFs of Leprdb/db mice. MCP-1-supplemented control plasma increased the expression of adiponectin, CCAAT-enhancer-binding protein α (C/EBPα), dipeptidyl peptidase 4 (DPP4), IL-33, and PDGFα mRNA and the expression of adiponectin protein as well as PPARγ of SVFs and the expression of PPARγ mRNA in adipose tissue macrophages (ATMs). Injection of MCP-1-supplemented plasma into adipose tissue of Leprdb/db mice increased the expression of IL-33 and Col3a1 mRNA in SVFs and IL-33, FABP4, PDGFα, PPARγ and PPARγ2 of ATMs, protein expression of adiponectin and PPARγ of SVFs, and plasma adiponectin levels, as well as DPP4 activity. In conclusion, our results demonstrate that control plasma decreases adipogenesis and increases IL-10, and decreases IL-33, pJNK, and pNF-κB in adipose tissue. MCP-1-supplemented plasma enhances adipogenesis-related gene expression in SVFs and adiponectin levels, which may be mediated through an increase of IL-33 and PPARγ. Thus, our findings suggest that MCP-1-supplemented plasma represents a novel therapy to stimulate local adipogenesis and systemic adiponectin levels.


Subject(s)
Adiponectin , Chemokine CCL2 , Animals , Mice , Adipogenesis/genetics , Adiponectin/genetics , Adiponectin/metabolism , Chemokine CCL2/genetics , Chemokine CCL2/metabolism , Dipeptidyl Peptidase 4/genetics , Gene Expression , Interleukin-10/genetics , Interleukin-33/genetics , PPAR gamma/genetics , PPAR gamma/metabolism , RNA, Messenger/metabolism
2.
Respir Res ; 22(1): 159, 2021 May 22.
Article in English | MEDLINE | ID: mdl-34022899

ABSTRACT

BACKGROUND: Patients in intensive care units (ICUs) often received broad-spectrum antibiotic treatment and Acinetobacter baumannii (A.b.) and Pseudomonas aeruginosa (P.a.) were the most common pathogens causing ventilator-associated pneumonia (VAP). This study aimed to examine the effects and mechanism of mechanical ventilation (MV) on A.b.-induced lung injury and the involvement of alveolar macrophages (AMs). METHODS: C57BL/6 wild-type (WT) and c-Jun N-terminal kinase knockout (JNK1-/-) mice received MV for 3 h at 2 days after nasal instillation of A.b., P.a. (1 × 106 colony-forming unit, CFU), or normal saline. RESULTS: Intranasal instillation of 106 CFU A.b. in C57BL/6 mice induced a significant increase in total cells and protein levels in the bronchoalveolar lavage fluid (BALF) and neutrophil infiltration in the lungs. MV after A.b. instillation increases neutrophil infiltration, interleukin (IL)-6 and vascular cell adhesion molecule (VCAM) mRNA expression in the lungs and total cells, IL-6 levels, and nitrite levels in the BALF. The killing activity of AMs against A.b. was lower than against P.a. The diminished killing activity was parallel with decreased tumor necrosis factor-α production by AMs compared with A.b. Inducible nitric oxide synthase inhibitor, S-methylisothiourea, decreased the total cell number in BALF on mice receiving A.b. instillation and ventilation. Moreover, MV decreased the A.b. and P.a. killing activity of AMs. MV after A.b. instillation induced less total cells in the BALF and nitrite production in the serum of JNK1-/- mice than those of WT mice. CONCLUSION: A.b. is potent in inducing neutrophil infiltration in the lungs and total protein in the BALF. MV enhances A.b.-induced lung injury through an increase in the expression of VCAM and IL-6 levels in the BALF and a decrease in the bacteria-killing activity of AMs. A lower inflammation level in JNK1-/- mice indicates that A.b.-induced VAP causes lung injury through JNK signaling pathway in the lungs.


Subject(s)
Acinetobacter Infections/enzymology , Acinetobacter baumannii/pathogenicity , Lung/enzymology , Mitogen-Activated Protein Kinase 8/metabolism , Pneumonia, Ventilator-Associated/enzymology , Respiration, Artificial/adverse effects , Ventilator-Induced Lung Injury/enzymology , Acinetobacter Infections/microbiology , Acinetobacter Infections/pathology , Animals , Cells, Cultured , Disease Models, Animal , Interleukin-6/genetics , Interleukin-6/metabolism , Lung/microbiology , Lung/pathology , Macrophages, Alveolar/enzymology , Macrophages, Alveolar/microbiology , Male , Mice, Inbred C57BL , Mice, Knockout , Mitogen-Activated Protein Kinase 8/genetics , Neutrophil Infiltration , Nitric Oxide Synthase Type II/metabolism , Pneumonia, Ventilator-Associated/microbiology , Pneumonia, Ventilator-Associated/pathology , Signal Transduction , Tumor Necrosis Factor-alpha/metabolism , Vascular Cell Adhesion Molecule-1/genetics , Vascular Cell Adhesion Molecule-1/metabolism , Ventilator-Induced Lung Injury/microbiology , Ventilator-Induced Lung Injury/pathology
3.
J Transl Med ; 17(1): 304, 2019 09 05.
Article in English | MEDLINE | ID: mdl-31488203

ABSTRACT

BACKGROUND: Infection by antibiotic-resistant microorganisms is common in intensive care units and has become a global problem. Here, we determined the effect of aryl hydrocarbon receptor (AhR) stimulation on antibiotics-induced systemic defense impairment and its mechanisms. METHODS: C57BL/6 wild-type (WT) mice received combined antibiotics with or without Ahr ligands (tryptophan and indole), or dead Lactobacillus plantarum supplementation. The defense mechanisms against Pseudomonas aeruginosa infection in the lung were examined. RESULTS: Antibiotic treatments decreased the phagocytic activity, physiological activity, and the peroxynitrite production of alveolar macrophage (AMs). It also enhanced P. aeruginosa pneumonia-induced bacterial counts in the lung. Tryptophan and dead L. plantarum supplementation reversed antibiotic-induced intracellular adhesion molecule (ICAM) as well as IL-6 expression, and increased P. aeruginosa pneumonia-induced bacterial counts in the lung and increased phagocytic activity and peroxynitrite production of AMs. Moreover, these treatments reversed the antibiotics-induced reduction of Ahr expression, antibacterial proteins, reactive oxygen species (ROS) production, and NF-κB DNA binding activity of the intestinal mucosa and plasma IL-6 levels. P. aeruginosa counts increased and phagocytic activity of AMs and myeloperoxidase (MPO) activity decreased in intestinal IKKß depleted mice. Antibiotics, antibiotic with tryptophan feeding, or antibiotic with dead L. plantarum feeding treatments did not change the phagocytic activity and peroxynitrite production of AMs, plasma IL-6 levels, and the expression of Ahr of intestine in intestinal IKKß depleted mice. CONCLUSION: Antibiotic treatment impairs lung immune defenses by decreasing Ahr expression in the intestine and peroyxnitrite production of the AMs. Ahr ligands reverses antibiotic-induced lung defense against bacterial infection through intestinal ROS production and NF-κB activation. The gut is critical in maintaining lung defense mechanism through the intestinal IKKß pathways.


Subject(s)
I-kappa B Kinase/metabolism , Intestines/physiology , Lung/immunology , Receptors, Aryl Hydrocarbon/metabolism , Signal Transduction , Administration, Oral , Animals , Anti-Bacterial Agents/pharmacology , Colony Count, Microbial , Indoles/pharmacology , Intestinal Mucosa/drug effects , Intestinal Mucosa/metabolism , Intestines/drug effects , Lactobacillus plantarum/physiology , Ligands , Lung/drug effects , Macrophages, Alveolar/drug effects , Macrophages, Alveolar/metabolism , Mice, Inbred C57BL , NF-kappa B/metabolism , Peroxynitrous Acid/metabolism , Phagocytosis/drug effects , Pneumonia/microbiology , Pseudomonas aeruginosa/drug effects , Pseudomonas aeruginosa/growth & development , Pseudomonas aeruginosa/physiology , Reactive Oxygen Species/metabolism , Tryptophan/administration & dosage , Tryptophan/pharmacology
4.
J Transl Med ; 16(1): 225, 2018 08 13.
Article in English | MEDLINE | ID: mdl-30103798

ABSTRACT

BACKGROUND: Widespread use of antibiotics in the intensive care unit is a potential cause of the emergence of hospital-acquired pneumonia. This study determined whether Lactobacillus salivarius feeding could reverse antibiotic-induced lung defense impairment in a ventilator model. METHODS: C57BL/6 wild-type (WT) mice received mechanical ventilation for 3 h after intramuscular antibiotic treatment for 6 days. Treatment with dead Lactobacillus salivarius and fructo-oligosaccharides (FOS) feeding were used to stimulate antibacterial protein expression in the intestine. Reactive oxygen species (ROS) in the intestinal mucosa was detected using 2'7'-dichlorofluorescein diacetate. The peroxynitrite production of alveolar macrophages (AMs) was measured using dihydrorhodamine 123 oxidation assay. N-acetylcysteine (NAC), an ROS scavenger, was orally administered to mice receiving antibiotics with FOS feeding. RESULTS: Antibiotic treatment decreased Pseudomonas aeruginosa (PA) phagocytic activity and activity of AMs and protein expression of regenerating islet-derived protein 3ß (Reg3ß) as well as Toll-like receptor 4 (TLR4) in the intestinal mucosa in the ventilator model. Antibiotic treatment also decreased ROS production in the intestinal mucosa, peroxynitrite production of AMs, and RELMß expression as well as NF-κB DNA binding activity of the intestinal mucosa in WT mice but not in MyD88-/- mice. Treatment with dead L. salivarius or FOS feeding increased ROS production, bacterial killing activity, and protein expression of Reg3ß as well as TLR4 in the intestinal mucosa and reversed the inhibitory effects of antibiotics on PA phagocytic activity of AMs. CONCLUSION: Taken together with the finding that ablation of FOS-induced intestinal ROS using NAC decreased peroxynitrite production as well as PA phagocytic activity of AMs and protein expression of CRP-ductin, IL-17, Reg3ß, and RELMß in the intestinal mucosa, we conclude that commensal microflora plays a key role in stimulating lung immunity. Intestinal ROS plays a role as a predictive indicator and modulator of pulmonary defense mechanisms. Antibiotic treatment reduces lung defense against PA infection through the decrease in intestinal Reg3ß and TLR4 expression. Treatment with dead L. salivarius or FOS feeding reverses the antibiotic-induced lung defense impairment through the intestinal ROS/MyD88 pathways.


Subject(s)
Anti-Bacterial Agents/adverse effects , Ligilactobacillus salivarius/physiology , Lung/immunology , Ventilators, Mechanical , Acetylcysteine/pharmacology , Animals , DNA/metabolism , Hormones, Ectopic/metabolism , Intercellular Signaling Peptides and Proteins , Intestinal Mucosa/drug effects , Intestinal Mucosa/pathology , Lung/microbiology , Lung/pathology , Macrophages, Alveolar/drug effects , Macrophages, Alveolar/metabolism , Macrophages, Alveolar/pathology , Mice, Inbred C57BL , Myeloid Differentiation Factor 88/metabolism , NF-kappa B/metabolism , Neutrophil Infiltration/drug effects , Pancreatitis-Associated Proteins/metabolism , Peroxynitrous Acid/metabolism , Phagocytosis/drug effects , Pneumonia/complications , Protein Binding/drug effects , Pseudomonas aeruginosa/drug effects , Reactive Oxygen Species/metabolism , Toll-Like Receptor 4/metabolism
5.
Respir Res ; 17(1): 101, 2016 08 09.
Article in English | MEDLINE | ID: mdl-27506464

ABSTRACT

BACKGROUND: Pseudomonas aeruginosa (PA) is the single-most common pathogen of ventilator-associated pneumonia (VAP). Large quantities of PA in the trachea of ventilated patients are associated with an increased risk of death. However, the role of PA colonization in PA VAP-induced lung injury remains elusive. This study examined the effect and mechanism of PA colonization in VAP-induced lung injury. METHODS: C57BL/6 wild-type (WT) and c-Jun N-terminal kinase knockout (JNK1(-/-)) mice received mechanical ventilation for 3 h at 2 days after receiving nasal instillation of PA (1 × 10(6) colony forming unit) or normal saline. RESULTS: Intranasal instillation of PA or mechanical ventilation induced the expression of interleukin-6 (IL-6) in the lungs. Phospho-JNK protein expression in the lungs was significantly increased in mice receiving mechanical ventilation after PA instillation as compared with those receiving ventilation alone. Mechanical ventilation after PA instillation significantly increased the expression of tumor necrosis factor-α (TNF-α), IL-1ß, and macrophage inflammatory protein-2 (MIP-2) proteins; neutrophil sequestration; and TNF-α, IL-1ß, and IL-6 levels in the lungs of WT mice, but not in JNK1(-/-) mice. CONCLUSION: PA colonization plays an important role in PA VAP-induced lung injury through the induction of JNK1-mediated inflammation. PA-induced VAP causes lung injury through JNK signaling pathway in the lungs. JNK inhibition in ICU patients with higher percentages of PA colonization may reduce VAP-induced lung injury and mortality.


Subject(s)
Lung/microbiology , Pneumonia, Ventilator-Associated/microbiology , Pseudomonas Infections/microbiology , Pseudomonas aeruginosa/pathogenicity , Animals , Bronchoalveolar Lavage Fluid/chemistry , Bronchoalveolar Lavage Fluid/cytology , Chemokine CXCL2/metabolism , Disease Models, Animal , Interleukin-1beta/metabolism , Interleukin-6/metabolism , Lung/metabolism , Mice, Inbred C57BL , Mice, Knockout , Mitogen-Activated Protein Kinase 8/deficiency , Mitogen-Activated Protein Kinase 8/genetics , Neutrophil Infiltration , Phosphorylation , Pneumonia, Ventilator-Associated/genetics , Pneumonia, Ventilator-Associated/metabolism , Pneumonia, Ventilator-Associated/prevention & control , Pseudomonas Infections/genetics , Pseudomonas Infections/metabolism , Pseudomonas Infections/prevention & control , Tumor Necrosis Factor-alpha/metabolism
6.
Cytokine ; 63(1): 58-66, 2013 Jul.
Article in English | MEDLINE | ID: mdl-23623770

ABSTRACT

PURPOSE: Tumor necrosis factor (TNFα) is a proinflammatory cytokine and has been a target for intervention in human sepsis. However, inhibition of TNF-α with a high dose of a TNF-receptor fusion protein in patients with septic shock worsened patient survival. This study was designed to investigate whether blocking TNF-α enhances mortality in infected burn mice through the induction of IL-1ß. METHODS: WT or Tnfrsf1a(-/-) mice received Pseudomonas aeruginosa injection in the back at 8h after burn injury. The animals were sacrificed at 24h after burn and lung tissues were harvested and examined for determining myeloperoxidase (MPO) activity, pulmonary microvascular dysfunction, NF-κB DNA binding activity, and IL-1ß expression. Also, the lung and blood were harvested for bacterial count assay. RESULT: Thermal injury alone induced NF-κB DNA binding activity and neutrophil infiltration in the lung in WT but not in Tnfrsf1a(-/-) mice. A 50% total body surface area (TBSA) burn induced a significant increase of mortality in WT compared with Tnfrsf1a(-/-) mice. In contrast, P. aeruginosa injection with a 30% TBSA burn pretreatment enhanced IL-1ß expression, bacterial counts in lung and blood, pulmonary microvascular dysfunction, and mortality in Tnfrsf1a(-/-) mice compared with WT mice. Injection of the IL-1 receptor antagonist, Anakinra, reduced P. aeruginosa infection with burn pretreatment-induced blood bacterial counts, IL-1ß levels as well as permeability of lung, and mortality in Tnfrsf1a(-/-) mice. CONCLUSIONS: Our findings suggest that thermal injury induces lung NF-κB activation and neutrophil sequestration through TNFα signaling. However, blocking TNF-α enhances P. aeruginosa infection-induced lung damage in burn mice via induction of IL-1ß. Using an IL-1 receptor antagonist combined with the neutralization of TNF-α could be a useful strategy for decreasing P. aeruginosa infection-induced mortality in burn patients.


Subject(s)
Burns/microbiology , Burns/pathology , Interleukin-1beta/metabolism , Pseudomonas aeruginosa/physiology , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Animals , Colony Count, Microbial , DNA/metabolism , Humans , Interleukin 1 Receptor Antagonist Protein/pharmacology , Lung/drug effects , Lung/enzymology , Lung/microbiology , Lung/pathology , Male , Mice , Mice, Inbred C57BL , NF-kappa B/metabolism , Peroxidase/metabolism , Protein Binding/drug effects , Pseudomonas Infections/blood , Pseudomonas Infections/microbiology , Pseudomonas Infections/pathology , Pseudomonas Infections/physiopathology , Pseudomonas aeruginosa/drug effects , Receptors, Interleukin-1/antagonists & inhibitors , Receptors, Interleukin-1/metabolism , Receptors, Tumor Necrosis Factor, Type I/deficiency , Receptors, Tumor Necrosis Factor, Type I/metabolism , Signal Transduction/drug effects , Temperature , Tumor Necrosis Factor-alpha/metabolism
7.
J Surg Res ; 179(1): 106-14, 2013 Jan.
Article in English | MEDLINE | ID: mdl-22995661

ABSTRACT

BACKGROUND: Sepsis is an infectious process-induced generalized inflammatory response that mediates the excessive production of cytokines. However, anti-tumor necrosis factor (TNF)-α therapy has failed in decreasing mortality of sepsis patients due to undefined mechanisms. This study was designed to investigate whether absence of TNF receptor enhanced lung damage and mortality through toll-like receptors (TLRs) and inducible nitric oxide synthase (iNOS). MATERIALS AND METHODS: We injected Pseudomonas aeruginosa or lipopolysaccharide in the backs of wild-type, Tnfrsf1a(-/-) (deficient of TNF-α receptor 1), and TLR4(-/-) mice at 8 h after 30% total body surface area burn. The animals were sacrificed at 16 h after burn and lung tissues were harvested and examined for determining pulmonary microvascular dysfunction and interleukin (IL)-1ß, iNOS, and TLR4 expression. The blood of animals was harvested for bacterial count assay. The effect of S-methylisothiourea, an iNOS inhibitor, on P aeruginosa infection with thermal injury pretreatment-induced lung damage was also examined. RESULTS: P aeruginosa or lipopolysaccharide injection with thermal injury pretreatment enhanced TLR4, iNOS, and IL-1ß expression and pulmonary microvascular dysfunction in Tnfrsf1a(-/-) mice compared with wild-type mice. P aeruginosa infection with thermal injury pretreatment did not induce IL-1ß or iNOS expression and mortality in TLR4(-/-) mice. S-methylisothiourea treatment significantly decreased P aeruginosa infection with thermal injury pretreatment-induced lung injury, blood bacterial counts, pulmonary IL-1ß expression, and mortality in Tnfrsf1a(-/-) mice. CONCLUSIONS: Given that absence of the TNF-α receptor 1 is associated with increased lung permeability, we conclude that TNF-α decreases P aeruginosa infection-induced lung damage in burn mice through negative regulation of TLR4 as well as iNOS expression, and iNOS inhibitor might be useful in reversing anti-TNF-α therapy-induced lung injury in burn.


Subject(s)
Burns/complications , Lung Injury/drug therapy , Lung Injury/etiology , Nitric Oxide Synthase Type II/metabolism , Pseudomonas Infections/complications , Toll-Like Receptor 4/metabolism , Tumor Necrosis Factor-alpha/therapeutic use , Animals , Burns/epidemiology , Comorbidity , Enzyme Inhibitors/therapeutic use , Interleukin-1beta/metabolism , Isothiuronium/analogs & derivatives , Isothiuronium/therapeutic use , Lipopolysaccharides/adverse effects , Lung Injury/metabolism , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , Models, Animal , Nitric Oxide Synthase Type II/antagonists & inhibitors , Pseudomonas Infections/epidemiology , Pseudomonas aeruginosa , Receptors, Tumor Necrosis Factor, Type I/deficiency , Receptors, Tumor Necrosis Factor, Type I/genetics , Receptors, Tumor Necrosis Factor, Type I/metabolism , Toll-Like Receptor 4/deficiency , Toll-Like Receptor 4/genetics , Treatment Outcome
8.
J Biomed Sci ; 18: 68, 2011 Sep 10.
Article in English | MEDLINE | ID: mdl-21906393

ABSTRACT

BACKGROUND: The influence of the gut flora on lung inflammatory reaction against bacterial challenge remains undefined. This study was designed to investigate whether gut flora enhances lung defense against E.coli pneumonia through TLR4 signaling. METHODS: C3H/HeN (WT) mice and C3H/HeJ (TLR4 deficient) mice were treated with antibiotics in drinking water for 4 weeks to deplete gut commensal microflora. At week 3, drinking water was supplemented with lipopolysaccharide (LPS); a ligand for TLR4, to trigger TLRs in intestinal tract. At the end of 4th week, E.coli was injected to trachea to induce E.coli pneumonia. RESULTS: We found that commensal depletion by antibiotic pretreatment before E.coli pneumonia challenge induced a 30% decrease of MPO activity in the lung, a significant decrease of bacterial killing activity of alveolar macrophage, and bacterial counts in C3H/HeN mice but not in C3H/HeJ (TLR4 deficient) mice. LPS, a TLR4 ligand, supplementation during antibiotic pretreatment reversed these effects and decreased E.coli pneumonia-induced mortality in C3H/HeN mice. Furthermore, commensal depletion induced a suppression of NF-κB DNA binding activity and an increase of KC, MIP-2, IL-1ß expression in the lung in C3H/HeN mice but not in C3H/HeJ mice. CONCLUSIONS: Taken together with that commensal depletion increased E.coli pneumonia-induced mortality and LPS supplementation decreased it, we conclude that gut flora enhances bacterial clearance against E.coli pneumonia through TLR4.


Subject(s)
Escherichia coli Infections/immunology , Gastrointestinal Tract/microbiology , Immunity, Innate/immunology , Pneumonia, Bacterial/immunology , Toll-Like Receptor 4/immunology , Toll-Like Receptor 4/metabolism , Analysis of Variance , Animals , Blotting, Western , Bronchoalveolar Lavage , DNA Primers/genetics , Gastrointestinal Tract/immunology , Lung/cytology , Lung/immunology , Macrophages/immunology , Male , Mice , Peroxidase/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Specific Pathogen-Free Organisms , Toll-Like Receptor 4/genetics
9.
Inflammation ; 32(6): 372-8, 2009 Dec.
Article in English | MEDLINE | ID: mdl-19728064

ABSTRACT

NOD2, an intracellular sensor of bacteria, are linked to increased susceptibility to bacteria in Crohn's disease (CD). The NOD2 protein is expressed mainly by macrophages and dendritic cells. This study is to examine the role of NOD2 in the innate response of macrophages to bacterial challenge. First, peritoneal macrophages and alveolar macrophages were harvested from WT, Nod2(2939iC), as well as TLR4(-/-) mice and incubated with E. coli or P. aeruginosa. Bacterial killing activity; IL-1beta and TLR4 protein expression; NF-kappaB DNA binding activity assay; as well as IL-1beta, TNFalpha, TLR2, TLR4 and TLR9 mRNA expression of macrophages were examined. We found that alveolar macrophages and peritoneal macrophages of Nod2(2939iC) mice but not WT mice or TLR4(-/-) mice demonstrated a significant increase of E. coli killing activity. Bacterial challenge also induced a significant increase of pro-IL-1beta protein expression; NF-kappaB DNA binding activity; as well as IL-1beta and TNFalpha mRNA expression of the peritoneal macrophages in Nod2(2939iC) mice. Collectively, the increase of bacterial killing activity, IL-1beta expression, and NF-kappaB DNA binding activity of macrophages in Nod2(2939iC) mice suggests that NOD2 is a positive regulator of NF-kappaB/IL-1beta-mediated innate response to bacteria challenge in Crohn's disease.


Subject(s)
Macrophages, Alveolar/immunology , Macrophages, Alveolar/microbiology , Macrophages, Peritoneal/immunology , Macrophages, Peritoneal/microbiology , Mutation , NF-kappa B/metabolism , Nod2 Signaling Adaptor Protein/genetics , Pseudomonas aeruginosa/immunology , Animals , Crohn Disease/immunology , Crohn Disease/microbiology , Crohn Disease/pathology , DNA-Binding Proteins/genetics , DNA-Binding Proteins/metabolism , Immunity, Innate , Macrophages, Alveolar/metabolism , Macrophages, Peritoneal/metabolism , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , NF-kappa B/genetics , Nod2 Signaling Adaptor Protein/physiology , Pseudomonas aeruginosa/growth & development
SELECTION OF CITATIONS
SEARCH DETAIL
...