Tsutomu Mochizuki

Influence of Interleukin-10 on the Interleukin-1 Receptor Antagonist/Interleukin-1β Ratio in the Colonic Mucosa of Ulcerative Colitis

A decrease in the ratio of IL-1ra/IL-1β produced regionally by the colonic mucosa of patients with ulcerative colitis (UC) is believed to play a role in the pathogenesis of UC. To investigate factors influencing intramucosal IL-1ra/IL-1β ratios, we evaluated polymorphism of the IL-1ra gene and the production of mucosal cytokines in Japanese patients with UC. Colonic biopsy specimens of mucosal tissue were placed in organ cultures for 24 h. Then, the supernatant concentrations of IL-1β, IL-1ra, IL-8, IL-4, IL-10, and TGF-β were assayed by ELISA. Genomic DNA was extracted from patient peripheral blood samples, then IL-1ra gene polymorphism was determined using PCR amplification. The mucosa from patients with active stage UC showed a tendency toward a decreased IL-1ra/IL-1β ratio. In the resolving stage, IL-1ra/IL-1β ratios increased with increasing IL-10 and TGF-β concentrations. The addition of human recombinant IL-10 to the culture supernatants produced concentration-dependent inhibition of IL-1β. In Japanese patients with UC, the IL-1ra allele gene 2 phenotype had no effect on the IL-1ra/IL-1β ratio. Our findings suggest that a relative deficiency of IL-10 in patients with UC may contribute to persistent inflammatory changes.

Gastric carcinoid tumors without autoimmune gastritis in Japan: A relationship with Helicobacter pylori infection

In Japan, most cases of gastric carcinoid tumor (GCT) are unassociated with either autoimmune gastritis (AIG) showing type-A chronic atrophic gastritis (CAG-A) or Zollinger-Ellison syndrome (ZES). However, the pathogenesis of this tumor remains unknown. Recent studies have determined that Helicobacter pylori infection induces gastric carcinoid in Mongolian gerbils and that H. pylori lipopolysaccharide exerts a mitogenic effect on ECL cells. We examined five patients with histologically diagnosed GCT, 40 patients with H. pylori-positive gastric ulcer (Hp+GU), 24 patients with H. pylori-positive duodenal ulcer (Hp+DU), and 12 patients with AIG showing CAG-A topographically. We compared the prevalence of H. pylori infection, and the levels of gastrin and pepsinogen (PG) in the serum of patients with GCT with those of patients with Hp+GU, or Hp+DU, and AIG. We also investigated the histological characteristics of the tumor and the gastric corpus mucosa in the GCT patients. The levels of serum gastrin and PG I and II were measured using an RIA kit. In all five (100%) patients with GCT, H. pylori infection was present, without any evidence of AIG or ZES. The serum levels of gastrin in the GCT patients were higher than those in either Hp+GU or Hp+DU patients and lower than those in the AIG patients. In contrast, serum PG I levels and the PG I/II ratio were lower in the GCT group than in the Hp+GU or Hp+DU groups. Histologically, all GCTs were ECL cell tumors and peritumoral corporal mucosal atrophy was observed in four of the five patients with GCT. In conclusions, H. pylori infection and hypergastrinemia were found in the patients with GCT without AIG. This finding suggests that H. pylori infection may induce corporal mucosal atrophy and hypergastrinemia that can produce a GCT with time.

Elevation of TFF1 gene expression during healing of gastric ulcer at non-ulcerated sites in the stomach: Semiquantification using the single tube method of polymerase chain reaction

Background : The Trefoil factor family 1 (TFF1), one of the trefoil peptides, has been considered to play protective and reparative roles of experimentally induced ulcers in the stomach. However, the alteration of the TFF1 mRNA in the non‐ulcerated areas of living human gastric mucosa in gastric ulcer is not well known. We examined TFF1 gene expression at non‐ulcerated sites during the healing of a gastric ulcer by semiquantitative determination of the TFF1 mRNA.

Regional Differences on Production of Chemokines in Gastric Mucosa Between Helicobacter pylori-Positive Duodenal Ulcer and Gastric Ulcer

It is well known that antrum-predominantgastritis and pan-gastritis occurs in the patients withHelicobacter pylori-positive duodenal ulcer (DU) andgastric ulcer (GU), respectively. However, the role of chemokines in the pathogenesis of thesepathologies is unclear. We examined the regionaldifferences in mucosal chemokine production in patientswith DU and GU. The production of interleukin-8 (IL-8), growth-related gene (GRO) α, andmacrophage inflammatory protein (MIP)-1α wasgreater in the antrum than in the corpus in DU patients.In the patients with GU, monocyte chemoattractantprotein (MCP)-1 levels in the mucosa adjacent to ulcer weregreater than those away for the ulcer in the corpus. Thereduction in chemokine production occurring inassociation with the eradication of H. pylori differed between DU and GU patients in the antrum (IL-8,P = 0.0394; GROα, P = 0.0149; MIP-1α, P =0.0246; MCP-1, P = 0.0087). The data imply a differentpathogenesis may exist for the gastritis present in patients with DU and GU occurring in H.pylori-positive individuals.