vasoactive-intestinal-peptide and Helicobacter-Infections

It is suggested that different neuropeptides are actively involved in the pathogenesis of Helicobacter pylori (H. pylori)-induced gastritis acting as important effectors of the neuroimmune complex interactions, but the available data is limited and contradictory. The aim of this study was to determine whether the chronic infection generates changes in substance P (SP) and vasoactive intestinal peptide (VIP) gastric level and to evaluate the dependence of these potential effects on the degree of bacterial colonization or the severity of the inflammatory infiltrate. Therefore, immunohistochemical tests were performed to examine SP and VIP expression in mucosal nerve endings and myenteric neurons. Both SP and VIP levels were significantly higher in gastric samples of patients infected with H. pylori compared to uninfected individuals, confirming that these neuropeptides are neuroimmune modulators involved in the pathogenesis of H. pylori infection. Although their expression did not correlate with the intensity of mucosal inflammation nor with the bacterial density, we observed a strong association between SP neuronal level and the degree of myenteric ganglionitis, which in turn correlated with the severity of mucosal T-cell infiltration. These findings suggest that the mechanisms of neuroimmune cross-talk depend on some other factors that remain to be determined.

Topics: Adult; Cohort Studies; Enteric Nervous System; Female; Gastric Mucosa; Helicobacter Infections; Humans; Inflammation; Male; Retrospective Studies; Substance P; Vasoactive Intestinal Peptide

The protective effect of capsaicin-sensitive sensory nerve (CSSN) activation was recently demonstrated in human gastric mucosa. We here examined changes in neuropeptides, specifically Substance P (SP), calcitonin-gene related peptide (CGRP) and vasoactive intestinal peptide (VIP) in patients with chronic gastritis or ulcer. Furthermore changes in neprilysin levels, which hydrolyse these neuropeptides, were determined. Gastric biopsies were obtained from both lesion- and normal-appearing mucosa of 57 patients. The presence of H. pylori infection was verified with rapid urease assay. Neuronal and non-neuronal levels of SP, VIP, CGRP and neprilysin activity were determined in freshly frozen biopsies. Immunohistochemical localization of neprilysin was performed in 30 paraffin embedded specimens. We here found that neuronal SP levels decreased significantly in normally appearing mucosa of patients with gastritis while levels of non-neuronal SP increased in diseased areas of gastritis and ulcer. The presence of H. pylori led to further decreases of SP levels. The content of VIP in both disease-involved and uninvolved mucosa, and expression of neprilysin, markedly decreased in patients with gastritis or ulcer. Since VIP, as well as SP fragments, formed following hydrolysis with neprilysin is recognized to have gastroprotective effects, decreased levels of VIP, SP and neprilysin may predispose to cellular damage.

Topics: Adult; Calcitonin Gene-Related Peptide; Duodenal Ulcer; Female; Gastric Mucosa; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Neprilysin; Neurons; Peptic Ulcer; Substance P; Ulcer; Vasoactive Intestinal Peptide; Young Adult

Citrus lemon (CL) belongs to Rutaceae family and is popularly known in Brazil as limão siciliano. The phytochemical analysis of CL fruit bark essential oil showed two majority components, limonene (LIM) and β-pinene (PIN). This study aimed to evaluate the gastroprotective mechanism of action from CL, LIM and PIN in ethanol- and indomethacin-induced gastric ulcers and its in vitro anti-Helicobacter pylori activity. After ethanol-induced gastric ulcer, the ulcer area was measured and the stomachs were destined to histology (HE and PAS), immunohistochemistry for HSP-70 and VIP and glutathione (GSH) measurement. The involvement of nitric oxide (NO) and sulfhydryl (SH) compounds was determined. The ulcer area for indomethacin-induced gastric ulcers was measured. PGE₂ concentration was biochemically measured. The minimum inhibitory concentration (MIC) against H. pylori was determined in vitro. In ethanol model, CL and LIM demonstrated 100% of gastroprotection, while PIN did not exert effective gastroprotection (53.26%). In the indomethacin model, CL and LIM offered effective gastroprotection but PIN did not show gastroprotective effect. The gastric ulcer area of rats pretreated with NO-synthase inhibitor or SH-blocker was decreased in comparison to the control group. The MIC obtained for CL was 125 μg/mL, for LIM was 75 μg/mL and for PIN was 500 μg/mL. The gastroprotective effect of CL and LIM was involved with increasing in mucus secretion, HSP-70 and VIP, but not with GSH, NO or SH compounds. CL gastroprotective mechanism is involved with PGE₂. PIN did not present gastroprotective activity.

Topics: Animals; Bicyclic Monoterpenes; Bridged Bicyclo Compounds; Citrus; Cyclohexenes; Dinoprostone; Disease Models, Animal; Drug Synergism; Glutathione; Helicobacter Infections; Helicobacter pylori; HSP70 Heat-Shock Proteins; Immunohistochemistry; Limonene; Male; Microbial Sensitivity Tests; Monoterpenes; Nitric Oxide; Plant Oils; Protective Agents; Rats; Rats, Wistar; Stomach Ulcer; Sulfhydryl Compounds; Terpenes; Vasoactive Intestinal Peptide

Several neuropeptides were supposed to take place in the protection of gastric mucosa and play role in the development of gastritis.. To investigate morphological relationship between nerve fibres and immunocytes, to find out if these cells synthetize some neuropeptides and if there is there any co-existence with TNF-α and NFκ-B.. Immunohistochemical, confocal laser microscopic methods were used to investigate nerve fibres, immunocompetent cells in control and gastritis mucosa.. The number of neuropeptide-containing nerve fibres increased significantly. In control stomach the number of lymphocytes, plasma cells, and mast cells was low and showed no immunoreactivity for neuropeptide antibodies. However, in gastritis, some of the immunocompetent cells were immunoreactive for SP and for NPY. Some of the SP immunoreactive cells showed also positive reaction for TNF-α and NFκ-B. The distance between nerve fibres and immunocytes was 1 µm or less.. The increase of neuropeptides released from nerve fibres and immunocompetent cells can take part in neurogenic inflammation and generate chronic gastritis.

Topics: Gastric Mucosa; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Immunohistochemistry; Lymphocytes; Mast Cells; Microscopy, Confocal; Nerve Fibers; Neuropeptide Y; NF-kappa B; Substance P; Tumor Necrosis Factor-alpha; Vasoactive Intestinal Peptide

To investigate the effect of Helicobacter pylori (H. pylori) infection on neuronal expressions in the stomach and spinal cord of mice so as to explain dyspepsia symptoms in H. pylori infected patients.. C57BL/6 female mice were studied at 2 weeks (acute infection group) and 12 weeks (chronic infection group) after H. pylori inoculation. Histological analyses for gastric inflammation and bacterial colonization were assessed by HE staining and Warthin-Starry staining. Fos, vasoactive intestinal polypeptide (VIP) and calcitonin gene-related peptide expressions (CGRP) were studied by immunohistochemistry.. H. pylori colonization was present mainly in pyloric region, but bacterial density was similar in both infected groups. The intensity of mucosal inflammation and activity was significantly higher in two infected groups than in those in the control group. The degree of mononuclear and polymorphonuclear cell infiltration in proventricular-glandular region and gastric corpus at 12 weeks after H. pylori inoculation was higher than that at 2 weeks after inoculation. The neuronal expressions of fos, VIP, and CGRP in the stomach and spinal cord were significantly more marked in the infected groups than in the control group, but there was no significant difference between two infected groups.. H. pylori infection induced different degrees of gastric mucosal inflammation in the murine model. Both early and chronic infection groups of mice showed enhanced neuronal expressions of fos, VIP and CGRP of stomach and spinal cord and these could form a basis for appearance of functional dyspeptic symptoms in patients with H. pylori infection.

Topics: Acute Disease; Animals; Calcitonin Gene-Related Peptide; Chronic Disease; Disease Models, Animal; Dyspepsia; Female; Gastritis; Helicobacter Infections; Helicobacter pylori; Immunohistochemistry; Mice; Neurons; Proto-Oncogene Proteins c-fos; Spinal Cord; Stomach; Vasoactive Intestinal Peptide

To investigate the effects of Helicobacter pylori (Hp) infection on neural expression in stomach and spinal cord, and to investigate the mechanism of functional dyspepsia after Hp infection.. Thirty-five female C57BL/6 mice were randomly divided into three groups: Group A (acute infection group, undergoing intragastric gavage of Hp suspension every other day for 3 times and then observed for 2 weeks, 15 mice), Group B (chronic infection group, undergoing intragastric gavage of Hp suspension every other day for 3 times and then observed for 2 weeks, 15 mice) and control group (undergoing intragastric gavage of normal saline every other day for 3 times and then observed for 2 weeks, 5 mice). After the observation the mice were killed and their stomachs were taken out to undergo gastric histology and bacterial colonization by HE staining and Warthin-Starry staining respectively. Their spinal cords of thoracic and lumbar segments were taken out too. Immunohistochemistry was used to detect the expression of Fos, vasoactive intestinal polypeptide (VIP), and calcitonin gene-related peptide (CGRP) in the stomach and spinal cord.. Three mice died 12 weeks after Hp infection. The rate of Hp colonization, mainly localized in pyloric gland region, was greater in Group B than in Group A, and was 0 in the control group. The severity of inflammation as shown by mononuclear cell infiltration, and activity of inflammation as shown by polymorphonuclear cell infiltration, in the pyloric gland region, proventriculus-glandular stomach region, and corpus gland region were more pronounced in Groups A and B, especially in Group B, than in the control group. The expression values of Fos, VIP, and CGRP in the stomach of Group A were 3.1 +/- 1.4, 4.5 +/- 1.8, and 2.4 +/- 0.8 respectively, all not significantly different from those of Group B (3.1 +/- 1.3, 3.5 +/- 1.6, and 2.2 +/- 0.8, all P > 0.05). The expression values of Fos, VIP, and CGRP in the spinal cord of Group A were 3.8 +/- 1.2, 3.2 +/- 1.5, and 2.2 +/- 0.6, all not significantly different from those of Group B (3.4 +/- 0.7, 2.6 +/- 1.2, and 2.5 +/- 1.1, all P > 0.05 for all). However, the neural expression values in both acute and chronic infection groups were significantly higher than those in the control group (2.4 +/- 0.9, 1.6 +/- 0.9, and 1.2 +/- 0.8 in stomach; and 2.0 +/- 1.6, 1.2 +/- 1.1, and 1.2 +/- 1.1 in spinal cord, P < 0.05 for all).. Hp infection, both acute and chronic, induces gastric histological changes such as inflammation and activity, and enhances the Fos, VIP, and CGRP expression in stomach and spinal cord, which can be a basis for symptom generation in dyspeptic patients with Hp infection.

Topics: Animals; Calcitonin Gene-Related Peptide; Female; Gastric Mucosa; Helicobacter Infections; Helicobacter pylori; Immunohistochemistry; Mice; Mice, Inbred C57BL; Neurons; Proto-Oncogene Proteins c-fos; Random Allocation; Spinal Cord; Stomach; Vasoactive Intestinal Peptide

Neuromuscular changes producing dysmotility and hyperalgesia may underlie symptom generation in functional gastrointestinal disorders. We investigated whether chronic Helicobacter pylori-induced gastritis causes neuromuscular dysfunction.. In vitro muscle contractility and acetylcholine release were evaluated in mice before and after H. pylori eradication. H. pylori colonization and gastritis were graded histologically. Substance P (SP)-, vasoactive intestinal polypeptide (VIP)-, and calcitonin gene-related peptide (CGRP) immunoreactivity (IR) and macrophages were studied by immunohistochemistry.. In Balb/c mice, chronic H. pylori infection did not affect muscle function but augmented antral relaxation after nerve electric field stimulation. Infected mice had lower acetylcholine release by electric field stimulation and had higher density of SP-, CGRP-, and VIP-IR nerves in the stomach and of SP- and CGRP-IR in the spinal cord. Cholinergic nerve dysfunction worsened progressively and was associated with increasing macrophage and mononuclear but not polymorphonuclear infiltrate or bacterial colonization. SCID mice had unchanged acetylcholine release despite high H. pylori colonization and macrophage infiltration. Eradication of H. pylori normalized functional and morphologic abnormalities except for increased density of gastric SP- and CGRP-IR nerves.. H. pylori infection induces functional and morphologic changes in the gastric neural circuitry that are progressive and lymphocyte dependent, and some persist after H. pylori eradication. The data have direct implications regarding the role of H. pylori infection in functional dyspepsia.

Topics: Acetylcholine; Animals; Calcitonin Gene-Related Peptide; Disease Models, Animal; Enteric Nervous System; Female; Gastritis; Helicobacter Infections; Helicobacter pylori; Immunohistochemistry; Macrophages; Mice; Mice, Inbred BALB C; Mice, SCID; Muscle Contraction; Specific Pathogen-Free Organisms; Spinal Cord; Stomach; Substance P; Vasoactive Intestinal Peptide

Topics: Animals; Dyspepsia; Gastrointestinal Motility; Helicobacter Infections; Helicobacter pylori; Humans; Inflammation; NG-Nitroarginine Methyl Ester; Nitric Oxide Synthase; Nitric Oxide Synthase Type I; Vasoactive Intestinal Peptide