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Clinical and Vaccine Immunology : CVI May 2010The objective of this study was to investigate the effects of glucose-based peritoneal dialysis (PD) fluids and icodextrin-based PD fluids on the expression of Toll-like...
Glucose-based peritoneal dialysis fluids downregulate toll-like receptors and trigger hyporesponsiveness to pathogen-associated molecular patterns in human peritoneal mesothelial cells.
The objective of this study was to investigate the effects of glucose-based peritoneal dialysis (PD) fluids and icodextrin-based PD fluids on the expression of Toll-like receptor 2 (TLR2)/TLR4 and subsequent ligand-induced mitogen-activated protein kinase (MAPK) and NF-kappaB signaling and tumor necrosis factor alpha (TNF-alpha) and interleukin-1beta (IL-1beta) mRNA expression in human peritoneal mesothelial cells (HPMCs). A human peritoneal mesothelial cell line (HMrSV5) was stimulated with glucose-based and icodextrin-based peritoneal dialysis fluids. Cell viability was assessed using MTT [3-(4,5-dimethylthiazolyl)-2,5-diphenyl-2H-tetrazolium bromide]. TLR2/TLR4 expression was determined by real-time PCR, Western blotting, and an immunofluorescence assay. In addition, cells were pretreated with different PD solutions and then incubated with Pam3CSK4 or lipopolysaccharide (LPS), and the degrees of MAPK and NF-kappaB activation were reflected by detecting the phosphorylation levels of extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun N-terminal kinase (JNK), p38, and p65, using a Western blot method. TNF-alpha and IL-1beta mRNA expression was measured by real-time PCR. Glucose-based peritoneal dialysis fluids suppressed the expression of TLR2 and TLR4 proteins in HPMCs. Challenge of cells with either Pam3CSK4 or LPS resulted in impaired TNF-alpha and IL-1beta production. Moreover, reduced TLR2 and TLR4 levels in glucose-based peritoneal dialysis solution-treated mesothelial cells were accompanied by reduced p42/44 (ERK1/2), JNK, p38 MAPK, and NF-kappaB p65 phosphorylation upon TLR ligand engagement. No significant changes in MAPK and NF-kappaB signaling and TNF-alpha and IL-1beta mRNA expression were observed in icodextrin-based PD solution-treated mesothelial cells. Glucose-based PD solution, but not icodextrin-based PD solution, downregulates expression of TLR2/TLR4 by human peritoneal mesothelial cells and triggers hyporesponsiveness to pathogen-associated molecular patterns.
Topics: Blotting, Western; Cell Line; Cell Survival; Chromogenic Compounds; Cytokines; Dialysis Solutions; Epithelial Cells; Fluorescent Antibody Technique, Direct; Glucans; Glucose; Humans; Icodextrin; Peritoneal Dialysis; Peritoneum; Reverse Transcriptase Polymerase Chain Reaction; Signal Transduction; Tetrazolium Salts; Toll-Like Receptor 2; Toll-Like Receptor 4
PubMed: 20200188
DOI: 10.1128/CVI.00453-09 -
Fertility and Sterility Jun 2012To evaluate inflammatory/angiogenic cytokines-interleukin-1β (IL-1β), IL-6, IL-8, IL-12, interferon-γ (IFN-γ), tumor necrosis factor (TNF), and vascular endothelial...
OBJECTIVE
To evaluate inflammatory/angiogenic cytokines-interleukin-1β (IL-1β), IL-6, IL-8, IL-12, interferon-γ (IFN-γ), tumor necrosis factor (TNF), and vascular endothelial growth factor A (VEGF-A)-in the peritoneal fluid of patients with endometriosis in relation to the occurrence and severity of pelvic adhesions and in control women without pelvic pathology.
DESIGN
Case-control study.
SETTING
University research institution and hospital.
PATIENT(S)
Sixty-five women with laparoscopically and histopathologically confirmed endometriosis, including 40 women with pelvic adhesions, and 37 control women without pelvic pathology.
INTERVENTION(S)
Peritoneal fluid aspirated during routine diagnostic laparoscopic examination.
MAIN OUTCOME MEASURE(S)
Cytokines evaluated in the peritoneal fluid via specific enzyme-linked immunosorbent assays.
RESULT(S)
Endometriosis and the revised American Fertility Society score of this disease were associated with statistically significantly increased levels of peritoneal IL-6 and IL-8 whereas the incidence and score of endometriosis-related pelvic adhesions were negatively associated with increased levels of VEGF-A. Notably, the concentration of VEGF-A predicted adhesion development and severity after adjustment for endometriosis severity. The adhesion score also correlated with increased levels of IL-6; however, after adjustment for endometriosis severity, the effect of this cytokine was no longer statistically significant.
CONCLUSION(S)
Increased levels of VEGF-A may be associated with a decreased rate of pelvic adhesion formation in the course of endometriosis.
Topics: Ascitic Fluid; Case-Control Studies; Cytokines; Endometriosis; Female; Humans; Interferon-gamma; Interleukin-12; Interleukin-1beta; Interleukin-6; Interleukin-8; Peritonitis; Severity of Illness Index; Tissue Adhesions; Tumor Necrosis Factor-alpha; Vascular Endothelial Growth Factor A
PubMed: 22542989
DOI: 10.1016/j.fertnstert.2012.03.057 -
Scientific Reports Jul 2017Peritonitis remains a major cause of morbidity and mortality during chronic peritoneal dialysis (PD). Glucose-based PD fluids reduce immunological defenses in the... (Randomized Controlled Trial)
Randomized Controlled Trial
Peritonitis remains a major cause of morbidity and mortality during chronic peritoneal dialysis (PD). Glucose-based PD fluids reduce immunological defenses in the peritoneal cavity. Low concentrations of peritoneal extracellular glutamine during PD may contribute to this immune deficit. For these reasons we have developed a clinical assay to measure the function of the immune-competent cells in PD effluent from PD patients. We then applied this assay to test the impact on peritoneal immune-competence of PD fluid supplementation with alanyl-glutamine (AlaGln) in 6 patients in an open-label, randomized, crossover pilot trial (EudraCT 2012-004004-36), and related the functional results to transcriptome changes in PD effluent cells. Ex-vivo stimulation of PD effluent peritoneal cells increased release of interleukin (IL) 6 and tumor necrosis factor (TNF) α. Both IL-6 and TNF-α were lower at 1 h than at 4 h of the peritoneal equilibration test but the reductions in cytokine release were attenuated in AlaGln-supplemented samples. AlaGln-supplemented samples exhibited priming of IL-6-related pathways and downregulation of TNF-α upstream elements. Results from measurement of cytokine release and transcriptome analysis in this pilot clinical study support the conclusion that suppression of PD effluent cell immune function in human subjects by standard PD fluid is attenuated by AlaGln supplementation.
Topics: Adult; Aged; Cross-Over Studies; Cytokines; Dialysis Solutions; Dipeptides; Feasibility Studies; Female; Gene Expression Profiling; Humans; Male; Middle Aged; Peritoneum; Pilot Projects; Renal Dialysis; Transcriptome
PubMed: 28740213
DOI: 10.1038/s41598-017-05872-2 -
International Journal of Molecular... Sep 2016Postoperative intra-abdominal adhesion is a very common complication after abdominal surgery. One clinical problem that remains to be solved is to identify an ideal...
Postoperative intra-abdominal adhesion is a very common complication after abdominal surgery. One clinical problem that remains to be solved is to identify an ideal strategy to prevent abdominal adhesions. Keratinocyte growth factor (KGF) has been proven to improve the proliferation of mesothelial cells, which may enhance fibrinolytic activity to suppress postoperative adhesions. This study investigated whether the combined administration of KGF and a sodium hyaluronate (HA) gel can prevent intra-abdominal adhesions by improving the orderly repair of the peritoneal mesothelial cells. The possible prevention mechanism was also explored. The cecum wall and its opposite parietal peritoneum were abraded after laparotomy to induce intra-abdominal adhesion formation. Animals were randomly allocated to receive topical application of HA, KGF, KGF + HA, or normal saline (Control). On postoperative day 7, the adhesion score was assessed with a visual scoring system. Masson's trichrome staining, picrosirius red staining and hydroxyproline assays were used to assess the magnitude of adhesion and tissue fibrosis. Cytokeratin, a marker of the mesothelial cells, was detected by immunohistochemistry. The levels of tissue plasminogen activator (tPA), interleukin-6 (IL-6), and transforming growth factor β1 (TGF-β1) in the abdominal fluid were determined using enzyme-linked immunosorbent assays (ELISAs). Western blotting was performed to examine the expression of the TGF-β1, fibrinogen and α-smooth muscle actin (α-SMA) proteins in the rat peritoneal adhesion tissue. The combined administration of KGF and HA significantly reduced intra-abdominal adhesion formation and fibrin deposition and improved the orderly repair of the peritoneal mesothelial cells in the rat model. Furthermore, the combined administration of KGF and HA significantly increased the tPA levels but reduced the levels of IL-6, tumor necrosis factor α (TNF-α) and TGF-β1 in the abdominal fluid. The expression levels of TGF-β1, fibrinogen and α-SMA protein and mRNA in the rat peritoneum or adhesion tissues were also down-regulated following the combined administration of KGF and HA. The combined administration of KGF and HA can significantly prevent postoperative intra-abdominal adhesion formation by maintaining the separation of the injured peritoneum and promoting mesothelial cell regeneration. The potential mechanism may be associated with rapid mesothelial cell repair in the injured peritoneum. This study suggests that combined administration of KGF and HA may be a promising pharmacotherapeutic strategy for preventing abdominal adhesions, which is worth further study, and has potential value in clinical applications.
Topics: Actins; Animals; Collagen Type I; Disease Models, Animal; Down-Regulation; Epithelium; Fibrinogen; Fibroblast Growth Factor 7; Gels; Hyaluronic Acid; Interleukin-1beta; Interleukin-6; Peritoneum; Postoperative Care; RNA, Messenger; Rats; Regeneration; Tissue Adhesions; Tissue Plasminogen Activator; Transforming Growth Factor beta1
PubMed: 27669222
DOI: 10.3390/ijms17101611 -
The proto-oncogene c-Fos transcriptionally regulates VEGF production during peritoneal inflammation.Kidney International Dec 2013Vascular endothelial growth factor (VEGF) and transforming growth factor-β1 (TGF-β1) are key mediators of adverse peritoneal membrane remodeling in peritoneal dialysis...
Vascular endothelial growth factor (VEGF) and transforming growth factor-β1 (TGF-β1) are key mediators of adverse peritoneal membrane remodeling in peritoneal dialysis eventually leading to ultrafiltration failure. Both are pleiotropic growth factors with cell type-dependent regulation of expression and biological effects. Here we studied regulation of TGF-β1-induced VEGF expression in human peritoneal mesothelial cells in the absence or presence of proinflammatory stimuli, tumor necrosis factor-α (TNF-α) or interleukin-1β (IL-1β). Quiescent human peritoneal mesothelial cells secreted only trace amounts of VEGF. Stimulation with TGF-β1 resulted in time- and dose-dependent increases in VEGF mRNA expression and protein release. TNF-α and IL-1β alone had minimal effects but acted in synergy with TGF-β1. Combined stimulation led to induction of transcription factor c-Fos and activation of the VEGF promoter region with high-affinity binding sites for c-Fos. Inhibition of c-Fos by small interfering RNA interference or by pharmacological blockade with SR-11302 decreased VEGF promoter activity and downregulated its expression and release. Exposure of human peritoneal mesothelial cells to dialysate effluent containing increased levels of TGF-β1, TNF-α, and IL-1β obtained during peritonitis resulted in a dose-dependent VEGF induction that was significantly attenuated by SR-11302. Thus, dialysate TGF-β1, IL-1β, and TNF-α act through c-Fos to synergistically upregulate VEGF production in peritoneal mesothelium and may represent an important regulatory link between inflammation and angiogenesis in the peritoneal membrane.
Topics: Binding Sites; Cells, Cultured; Dialysis Solutions; Epithelial Cells; Humans; Inflammation Mediators; Interleukin-1beta; Peritoneum; Peritonitis; Promoter Regions, Genetic; Proto-Oncogene Mas; Proto-Oncogene Proteins c-fos; RNA Interference; RNA, Messenger; Time Factors; Transcription, Genetic; Transfection; Transforming Growth Factor beta1; Tumor Necrosis Factor-alpha; Up-Regulation; Vascular Endothelial Growth Factor A
PubMed: 23760290
DOI: 10.1038/ki.2013.217 -
Singapore Medical Journal Sep 2019A 92-year-old woman presented to the emergency department with urinary symptoms, fever and suprapubic tenderness. Her inflammatory markers were raised. Urine and blood...
A 92-year-old woman presented to the emergency department with urinary symptoms, fever and suprapubic tenderness. Her inflammatory markers were raised. Urine and blood cultures were negative. Computed tomography performed to look for a source of sepsis showed distension of the uterine cavity with high-attenuation fluid, an air-fluid level and gas locules along the uterine wall. The causes, clinical presentation and imaging features of pyometra are discussed.
Topics: Aged, 80 and over; China; Diabetes Complications; Emergency Service, Hospital; Female; Fever; Humans; Hypertension; Inflammation; Leiomyoma; Middle Aged; Myocardial Ischemia; Necrosis; Peritonitis; Pyometra; Sepsis; Tomography, X-Ray Computed; Ultrasonography; Uterus
PubMed: 31570949
DOI: 10.11622/smedj.2019113 -
Oxidative Medicine and Cellular... 2021Postoperative peritoneal adhesions are considered the major complication following abdominal surgeries. The primary clinical complications of peritoneal adhesion are...
Postoperative peritoneal adhesions are considered the major complication following abdominal surgeries. The primary clinical complications of peritoneal adhesion are intestinal obstruction, infertility, pelvic pain, and postoperative mortality. In this study, regarding the anti-inflammatory and antioxidant activities of we aimed to evaluate the effects of on the prevention of postsurgical-induced peritoneal adhesion. Male Wistar-Albino rats were used to investigate the preventive effects of extract (0.5%, 0.25% and 0.125% /) against postsurgical-induced peritoneal adhesion compared to pirfenidone (PFD, 7.5% /). We also investigated the protective effects of PFD (100 g/ml) and extract (100, 200, and 400 g/ml) in TGF-1-induced fibrotic macrophage polarization. The levels of cell proliferation and oxidative, antioxidative, inflammatory and anti-inflammatory, fibrosis, and angiogenesis biomarkers were evaluated both and models. extract ameliorates postoperational-induced peritoneal adhesion development by attenuating oxidative stress [malondialdehyde (MDA)]; inflammatory mediators [interleukin- (IL-) 6, tumour necrosis factor- (TNF-) , and prostaglandin E (PGE)]; fibrosis [transforming growth factor- (TGF-) 1, IL-4, and plasminogen activator inhibitor (PAI)]; and angiogenesis [vascular endothelial growth factor (VEGF)] markers, while propagating antioxidant [glutathione (GSH)], anti-inflammatory (IL-10), and fibrinolytic [tissue plasminogen activator (tPA)] markers and tPA/PAI ratio. In a cellular model, we revealed that the extract, without any toxicity, regulated the levels of cell proliferation and inflammatory (TNF-), angiogenesis (VEGF), anti-inflammatory (IL-10), M1 [inducible nitric oxide synthase (iNOS)] and M2 [arginase-1 (Arg 1)] biomarkers, and iNOS/Arg-1 ratio towards antifibrotic M1 phenotype of macrophage, in a concentration-dependent manner. Taken together, the current study indicated that reduces peritoneal adhesion formation by modulating the macrophage polarization from M2 towards M1 cells.
Topics: Animals; Crocus; Disease Models, Animal; Humans; Male; Peritoneum; Postoperative Period; Rats; Therapeutic Irrigation
PubMed: 34956439
DOI: 10.1155/2021/5945101 -
Infection and Immunity Jan 1997Although the role of members of the Enterobacteriaceae and anaerobes in the pathogenesis of intra-abdominal infections has been extensively demonstrated, the role played...
Although the role of members of the Enterobacteriaceae and anaerobes in the pathogenesis of intra-abdominal infections has been extensively demonstrated, the role played by enterococci in these infections remains controversial. The pathophysiological mechanisms induced by enterococci in intra-abdominal infection were studied in a nonfatal model of peritonitis in rats by implanting a gelatin capsule containing Escherichia coli and Bacteroides fragilis with or without increasing concentrations of Enterococcus faecalis or heat-inactivated enterococci. The ability of the rat peritoneal cavity to sterilize itself after bacterial challenge was evaluated by quantifying the inflammatory response in the peritoneal cavity, reflected by both phagocyte and cytokine responses. Effects were evaluated 6, 12, and 24 h and 3 and 6 days after inoculation. On day 6 after inoculation, the highest enterococcal concentration (10(8) CFU/ml) was accompanied by significantly increased concentrations of E. coli in peritoneal fluid and peritoneal phagocytes when compared to other groups. In the first 12 h after inoculation, tumor necrosis factor and interleukin-6 concentrations were significantly increased in the peritoneal fluid of the animals that had received the highest inoculum of enterococci or heat-inactivated enterococci. In the late period of the study (3 and 6 days), significantly increased leukocyte counts were observed in the peritoneal fluid of these animals. These results suggest that E. faecalis somehow inhibited phagocytosis and intracellular killing of the other pathogens and also played an inflammatory role, which might account for the bacterial synergy observed in this model.
Topics: Animals; Bacteroidaceae Infections; Bacteroides fragilis; Cytokines; Enterococcus faecalis; Escherichia coli Infections; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Leukocyte Count; Male; Peritoneal Cavity; Peritonitis; Phagocytosis; Rats; Rats, Sprague-Dawley
PubMed: 8975904
DOI: 10.1128/iai.65.1.144-149.1997 -
Journal of the Formosan Medical... Oct 2015A rare but severe complication, intestinal necrosis, has been reported after sodium polystyrene sulfonate (SPS; Kayexalate) and sorbitol intake. Some case reports...
A rare but severe complication, intestinal necrosis, has been reported after sodium polystyrene sulfonate (SPS; Kayexalate) and sorbitol intake. Some case reports described bowel perforation following calcium polystyrene sulfonate (CPS; Kalimate) administration. We report a case of ileum and colon perforation following peritoneal dialysis-related peritonitis and high-dose Kalimate in a 59-year-old female patient. The patient had a history of hypertension, diabetes mellitus, and end-stage renal disease (ESRD). During hospitalization for peritoneal dialysis-related peritonitis, she developed hyperkalemia, and Kalimate was administered orally. However, severe abdominal distension and pain occurred just one day after Kalimate intake. An urgent surgery disclosed several perforations in the ileum and sigmoid colon. Pathology of the resected gut showed transmural necrosis and perforation with basophilic angulated crystals. The patient finally expired during hospitalization due to refractory septic shock.
Topics: Colon; Fatal Outcome; Female; Humans; Hyperkalemia; Ileum; Intestinal Perforation; Kidney Failure, Chronic; Middle Aged; Necrosis; Peritoneal Dialysis; Peritonitis; Polystyrenes; Shock, Septic; Sorbitol
PubMed: 23602017
DOI: 10.1016/j.jfma.2013.02.006 -
International Journal of... May 1995The levels of the eicosanoids leukotriene B4, prostaglandin E2, prostacycline and thromboxane B2, the cytokines interleukin-1 beta, interleukin-6 and tumour necrosis...
Levels of soluble intercellular adhesion molecule 1, eicosanoids and cytokines in ascites of patients with liver cirrhosis, peritoneal cancer and spontaneous bacterial peritonitis.
The levels of the eicosanoids leukotriene B4, prostaglandin E2, prostacycline and thromboxane B2, the cytokines interleukin-1 beta, interleukin-6 and tumour necrosis factor-alpha and soluble intercellular adhesion molecule 1 were measured in ascites and plasma samples of patients with liver cirrhosis (53), peritoneal cancer (26) and spontaneous bacterial peritonitis (10) to assess their value as a possible diagnostic and prognostic parameter in the course of the disease. Soluble intercellular adhesion molecule 1, of the eicosanoids prostaglandin E2 and leukotriene B4, and the protein concentration in ascites were all significantly elevated in ascites of patients with peritoneal cancer in comparison to ascites of patients with liver cirrhosis. In ascites of patients with spontaneous bacterial infection interleukin-6 concentration was significantly elevated and the protein concentration was significantly lower in comparison to the other two groups. None of these parameters, however, seems to be of practical use as a diagnostic parameter, as there is an overlap between all the levels of these mediators in ascites of liver cirrhosis, peritoneal cancer and spontaneous bacterial peritonitis group. Soluble intercellular adhesion molecule 1 levels were much higher in plasma than in ascites, in contrast to interleukin-6 levels which were much higher in ascites than in plasma. Soluble intercellular adhesion molecule 1 in ascites correlated with soluble intercellular adhesion molecule 1 in plasma (r = 0.6926, P = 0.0001). Soluble intercellular adhesion molecule 1, interleukin-6 and the number of polymorphonuclear cells in peritoneal fluid correlated during episodes of infection in patients with a peritonitis. For this reason soluble intercellular adhesion molecule 1 and interleukin-6 could be of prognostic value for patients with peritonitis.
Topics: Adult; Aged; Ascites; Bacterial Infections; Cohort Studies; Cytokines; Dialysis; Eicosanoids; Female; Humans; Immunoassay; Inflammation; Intercellular Adhesion Molecule-1; Liver Cirrhosis; Male; Middle Aged; Peritoneal Neoplasms; Peritonitis; Prognosis; Proteins; Statistics as Topic; Time Factors
PubMed: 7591361
DOI: 10.1016/0192-0561(95)00015-t