epidermal-growth-factor and Infections

Multiple sclerosis (MS) is a progressive neurodegenerative disease associated with increased infection rates, chronic inflammation, and premature death. Optimization of nutritional status via dietary supplementation may improve immune function in people suffering from MS and lead to decreased rates of infection. Fifteen individuals with a diagnosis of relapsing-remitting MS for an average of 12.4 years (SD =7.4; R = 2, 25) were enrolled in a one-year open-label clinical trial. Participants consumed a broad-spectrum dietary supplement regimen containing polysaccharides, phytochemicals, antioxidants, vitamins, and minerals three times per day. The occurrence of infections and a panel of cytokines, growth factors, and T- and B-cell subsets were assessed at baseline and 12 months. Seven female and 8 male participants with an average age of 51.3 years (SD =7.2; R = 38, 65) completed the study. At the end of the intervention, participants had fewer total infections (M = 7.9, SD =8.1 at baseline and M = 2.5, SD =4.3 at 12-month follow-up). At 12 months, IL-2, TNF-α, EGF, and CD95 + CD34+ significantly increased, while IL-1β significantly decreased. No major adverse effects were reported; only mild gastrointestinal intolerance was reported in four cases. A decreased occurrence of infection was observed in MS patients treated with 12 months of a polysaccharide-based multinutrient dietary supplement. Significant changes were also noted in several key biomarkers that would be physiologically favorable to the MS population. Thus, the results of this study suggest an immunomodulatory effect of the dietary supplement regimen studied.

Topics: Adult; Aged; Antigens, CD34; Biomarkers; Complementary Therapies; Cytokines; Dietary Supplements; Epidermal Growth Factor; fas Receptor; Female; Humans; Infections; Male; Micronutrients; Middle Aged; Multiple Sclerosis; Polysaccharides; T-Lymphocyte Subsets; Tumor Necrosis Factor-alpha

The MUC1 cell-surface mucin is highly expressed on the gastric mucosal surface, while MUC13 is highly expressed on the intestinal mucosal surface. Polymorphisms in both MUC1 and MUC13 have been linked to inflammatory bowel diseases. MUC1 can act as a decoy molecule on the apical cell surface of epithelial cells and thereby limit bacterial adherence, infection, and inflammation. In this study, we examined whether and how MUC1 and MUC13 modulate infectious and inflammatory signaling. Using gastrointestinal tissue from Muc1- or Muc13-deficient mice in ex vivo culture, MUC1 small interfering RNA (siRNA) silencing in MKN7 gastric epithelial cells, and MUC13 siRNA silencing in LS513 intestinal epithelial cells, we showed that loss of MUC1 increased chemokine secretion, whereas loss of MUC13 decreased chemokine secretion in response to tumor necrosis factor-α. Anti-inflammatory activity of MUC1 and pro-inflammatory activity of MUC13 were also seen after exposure to pathogens, NOD1 (nucleotide-binding oligomerisation domain-containing protein-1), and Toll-like receptor ligands. MUC1 and MUC13 both regulate chemokine secretion in gastrointestinal epithelial cells through a nuclear factor-κB-dependent pathway, although MUC13 modulation could also involve other pathways. Our studies demonstrate that MUC1 and MUC13 are important components of gastrointestinal homeostasis and that disruption or inappropriate expression of these mucins could predispose to infectious and inflammatory disease and inflammation-induced cancer.

Topics: Animals; Antigens, Surface; Cell Line; Chemokines; Epidermal Growth Factor; Gene Expression Regulation; Humans; Infections; Inflammatory Bowel Diseases; Intestinal Mucosa; Mice; Mice, 129 Strain; Mice, Knockout; Mucin-1; NF-kappa B; RNA, Small Interfering; Signal Transduction; Tumor Necrosis Factor-alpha

Neurogenesis has been described in limited regions of the adult mammalian brain. In this study, we showed that the ependymal layer of the 3rd ventricle is a neurogenic region in the adult rat brain. DiI labeling of the 3rd ventricle revealed that neural progenitor cells were derived from cells at the ependymal layer of the adult 3rd ventricle. The mitosis of these progenitor cells at the ependymal layer was promoted by bFGF administration. Combination of BrdU administration, nestin/GFAP immunohistochemistry, and labeling by GFP-recombinant adenoviral infection (vGFP) indicated that at least some tanycytes might be neural progenitor cells in the ependymal layer of the 3rd ventricle. Tracing by vGFP indicated that neural progenitor cells may have migrated from the 3rd ventricle to the hypothalamic parenchyma, where they were integrated into neural networks by forming synapses. In addition, some BrdU(+) neurons had immunoreactivity for orexin A in the hypothalamus. These results indicate that neural progenitor cells exist in the ependymal layer of the adult rat 3rd ventricle and that they may differentiate into neurons functioning in the hypothalamus.

Topics: Adenoviridae; Animals; Blotting, Western; Bromodeoxyuridine; Carbocyanines; Cell Count; Cell Death; Cell Differentiation; Cell Movement; Cells, Cultured; Drug Interactions; Ependyma; Epidermal Growth Factor; Female; Fibroblast Growth Factors; Glial Fibrillary Acidic Protein; Green Fluorescent Proteins; Hypothalamus; Imaging, Three-Dimensional; Immunohistochemistry; In Situ Nick-End Labeling; Infections; Intermediate Filament Proteins; Intracellular Signaling Peptides and Proteins; Male; Microscopy, Electron, Transmission; Mitosis; Nerve Tissue Proteins; Nestin; Neurons; Neuropeptides; Orexin Receptors; Orexins; Rats; Rats, Sprague-Dawley; Receptors, Fibroblast Growth Factor; Receptors, G-Protein-Coupled; Receptors, Neuropeptide; Sex Factors; Stem Cells; Third Ventricle

Bacterial translocation (BT) from the gastrointestinal tract to mesenteric lymph nodes (MLN) and other extraintestinal organs is an important source of infection in acute pancreatitis (AP). Epidermal growth factor (EGF), a peptide hormone with trophic effects on gut mucosa, has decreased intestinal mucosal injury in septic rats and decreased burn-induced BT in mice. The purpose of this study is to examine whether EGF could affect BT in acute necrotizing pancreatitis. Forty-eight male Sprague-Dawley rats (250-350 g) were studied. AP was induced in Group I and Group II by pressure injection of 3% taurocholate and trypsin into the biliopancreatic duct (1 ml/kg of body weight). Group III and Group IV underwent laparotomy without induction of acute pancreatitis. Group I rats received human recombinant EGF (100 micrograms/kg, subcutaneously twice daily) and Group II rats received a similar volume of 0.1% bovine serum albumin as a placebo postoperatively. Group III and Group IV received EGF and placebo, respectively. At 48 hr postoperatively, blood was drawn for culture and amylase determinations. Jejunum and ileum were obtained to measure mucosal protein content, mucosal thickness, villus height, and crypt depth. Specimens from MLN, spleen, liver, pancreas, and cecum were harvested for pathology and culture of gram positive (G+), gram negative (G-), and anaerobic bacteria. Ileal mucosal protein levels were increased significantly in Group I (1.96 +/- 0.14 mg/cm) compared to Group II (0.95 +/- 0.15 mg/cm intestinal segment) (P < 0.01). Jejunal and ileal mucosal thickness, villus height, and crypt depth in Group I were significantly increased when compared to Group II (P < 0.05). All 12 rats in Group II had BT to MLN compared to 58% (7 of 12 rats) in Group I (P < 0.05). Thirty-three percent (4 of 12 rats) had BT to distant sites such as pancreas, spleen, liver, and/or blood in Group I vs 83% (10 of 12 rats) in Group II (P < 0.05). EGF treatment minimizes intestinal damage, decreases BT to MLN and bacterial spread to distant sites, and may be beneficial in preventing septic complications in AP.

Topics: Acute Disease; Animals; Bacterial Translocation; Epidermal Growth Factor; Humans; Ileum; Infections; Intestinal Mucosa; Laparotomy; Lymph Nodes; Male; Mesentery; Pancreatitis; Proteins; Rats; Rats, Sprague-Dawley; Recombinant Proteins; Serum Albumin, Bovine

Our purpose was to evaluate the effects of known stimulants of prostaglandin production on cultured myometrial cells from women in labor with and without intrauterine infection.. Myometrial segments were obtained from 16 patients between 33 and 40 weeks' gestation who had been in labor for > or = 8 hours at cesarean delivery; 8 patients had clinical chorioamnionitis and 8 did not. Myometrial cells were isolated and grown in culture. Incubations were conducted with interleukin-1 beta, tumor necrosis factor-alpha, or epidermal growth factor. Prostaglandin E2, prostaglandin F2 alpha, and 6-keto-prostaglandin F1 alpha (the stable metabolite of prostacyclin) were measured by radioimmunoassay, and cellular protein was determined.. Cultured human myometrial cells from patients with and without prior intrauterine infection produced prostaglandins in response to interleukin-1 beta, tumor necrosis factor-alpha, and epidermal growth factor at a significantly increased rate (p<0.05 vs controls at and above 10 ng/ml of interleukin-1 beta, tumor necrosis factor-alpha, and epidermal growth factor). The major prostaglandin produced in response to each stimulant was 6-keto-prostaglandin F1 alpha; however, this response was attenuated in cells from patients with intrauterine infection.. Cultured human myometrial cells from patients with and without prior intrauterine infection respond to known stimulants of prostaglandin production. Prior intrauterine infection has no effect on baseline prostaglandin production, but the amount of prostacyclin produced as a response to cellular stimulants is decreased with prior intrauterine infection. This effect may have a role in regulating myometrial function in intrauterine infection.

Topics: 6-Ketoprostaglandin F1 alpha; Cells, Cultured; Cytokines; Dinoprost; Dinoprostone; Epidermal Growth Factor; Female; Humans; Infections; Interleukin-1; Myometrium; Pregnancy; Pregnancy Complications, Infectious; Prostaglandins; Tumor Necrosis Factor-alpha; Uterine Diseases

1. The effects of parenteral nutrition with or without glutamine supplementation and epidermal growth factor treatment (0.15 microgram/g body weight) was studied in the small bowel of septic rats after 4 days. 2. Septic rats infused with glutamine-supplemented parenteral nutrition with or without epidermal growth factor treatment survived sepsis significantly better than other septic rats given parenteral nutrition. The cumulative percentage of deaths over 4 days in septic rats infused with glutamine-supplemented parenteral nutrition was 20% (without epidermal growth factor) and 15% (with epidermal growth factor) compared with 50% in septic rats treated with parenteral nutrition without glutamine and 35% in septic rats given parenteral nutrition without glutamine but with epidermal growth factor treatment. 3. Glutamine-supplemented parenteral nutrition with or without epidermal growth factor treatment resulted in improved nitrogen balance in septic rats. The cumulative nitrogen balance over the 4 day period was the least negative as compared with other groups of septic rats. 4. Septic rats given parenteral nutrition with glutamine, epidermal growth factor or glutamine and epidermal growth factor exhibited marked increases in intestinal net rates of utilization of glutamine (P less than 0.001) and production of ammonia (P less than 0.001) compared with septic rats given parenteral nutrition without glutamine and/or epidermal growth factor treatment. 5. Septic rats given parenteral nutrition with glutamine, epidermal growth factor or glutamine and epidermal growth factor exhibited significant increases in jejunal wet weight (by 32.4-40.6%), DNA content (by 24.2-34.7%), protein content (by 29.1-50.0%), villus height (by 16.3-26.4%) and crypt depth (by 20.3-29.6%) compared with other groups of septic rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Ammonia; Animals; DNA; Epidermal Growth Factor; Glutamine; Infections; Intestinal Diseases; Intestinal Mucosa; Intestine, Small; Male; Nitrogen; Protein Biosynthesis; Rats; Rats, Inbred Strains