Oral tolerance induced by enterobacteria altered the process of lymphocyte recruitment to intestinal microvessels: roles of endothelial cell adhesion molecules, TGF-beta and negative regulators of TLR signaling.

OBJECTIVE: Although enterobacteria are implicated in intestinal immune response, there has been no report on how intraluminal pathogens affect lymphocyte recruitment. The aim of this study was to determine how the presence of intestinal flora affects lymphocyte migration to intestine under physiological and lipopolysaccharide (LPS)-induced inflammatory conditions. METHODS: Interaction of T-cells with ileal microvessels was monitored by using an intravital microscope in mice under germ-free (GF) and specific pathogen-free (SPF) conditions. LPS was administered into either the peritoneal cavity or duodenum before lymphocyte injection. RESULTS: Adherence of T-cells was greater in SPF than in GF mice, indicating that the presence of enterobacteria upregulated migration under physiological conditions. Intraperitoneally administered LPS significantly increased the adherence of T-cells in both GF and SPF mice accompanied by the expression of adhesion molecules and proinflammatory cytokines. However, intraluminally administered LPS did not enhance the adherence of T-cells in SPF mice. A significant induction of increase in mRNA expression of IRAK-M, a negative regulator of TLR4 signaling, and transforming growth factor beta (TGF-beta), a regulatory cytokine, was observed in SPF mice after luminal LPS treatment. CONCLUSIONS: Tolerance to intraluminally administered LPS in the lymphocyte recruitment process was induced by enterobacteria, possibly via the induction of IRAK-M and TGF-beta.

Omega-3 fatty acids exacerbate DSS-induced colitis through decreased adiponectin in colonic subepithelial myofibroblasts.

BACKGROUND: Although the immunoregulatory effects of omega-3 fatty acid and adiponectin have been postulated, their role in intestinal inflammation is controversial. The aim of this study was to determine whether dietary fat intake influences activity of colonic inflammation through modulating this system. METHODS: C57BL/6 mice received dextran sulfate sodium for induction of colitis. Mice were fed a control diet, omega-3 fat-rich diet, omega-6 fat-rich diet, or saturated fat-rich diet. Some mice were administered a peroxisome proliferator activated receptor-gamma; agonist, pioglitazone. Messenger RNA expression of adiponectin and its receptors were analyzed. Adiponectin expression in colonic mucosa of ulcerative colitis patients was also analyzed. RESULTS: The receptors for adiponectin were found to be ubiquitously expressed in epithelial cells, intraepithelial lymphocytes, lamina proprial mononuclear cells, and subepithelial myofibroblasts from colonic tissue, but adiponectin was only expressed in myofibroblasts. Induction of colitis significantly decreased the expression of adiponectin in colonic mucosa. The omega-3 fat diet group, but not the other fat diet groups, showed exacerbated colitis with a further decrease of adiponectin expression. Pioglitazone treatment ameliorated the level of decrease in adiponectin expression and improved colonic inflammation induced by the omega-3 fat-rich diet. In patients with ulcerative colitis, the expression level of adiponectin in colonic mucosa was also decreased compared with that in control mucosa. CONCLUSIONS: Adiponectin was found to be expressed in myofibroblasts. Adiponectin expression was significantly suppressed by induction of colitis, and aggravation of colitis after exposure to omega-3 fat may be due to a further decrease in the expression level of adiponectin.

[A case of Churg-Strauss syndrome discovered with hematemesis].

A 68-years-old Japanese woman was hospitalized emergently because of hemorrhagic gastric ulcer. For the hospitalization period, elevated levels of white blood cell count, eosinophilic leucocyte count, serum IgE and positive MPO-ANCA were recognized. With considering clinical course and these laboratory findings, we diagnosed Churg-Strauss syndrome (CSS). Steroid therapy in combination with cyclophosphamide was effective. CSS is a rare disease, but we should discriminate this disease when we encounter gastrointestinal bleeding of unknown etiology, especially PPI-resistant gastric ulcer.