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Mucosal changes in inflammatory bowel disease (IBD) are characterized by ulcerative lesions accompanied by a prominent infiltrate of inflammatory cells including lymphocytes, macrophages, and neutrophils and alterations in 5-hydroxytryptamine (5-HT)-producing enterochromaffin (EC) cells. Mechanisms involved in recruiting and activating these cells are thought to involve a complex interplay of inflammatory mediators. Studies in clinical and experimental IBD have shown the upregulation of various chemokines including monocyte chemottractant protein (MCP)-1 in mucosal tissues. However, precise information on the roles of this chemokine or the mechanisms by which it takes part in the pathogenesis of IBD are not clear. In this study, we investigated the role of MCP-1 in the development of hapten-induced experimental colitis in mice deficient in MCP-1. Our results showed a significant reduction in the severity of colitis both macroscopically and histologically along with a decrease in mortality in MCP-l-deficient mice compared with wild-type control mice. This was correlated with a downregulation of myeloperoxidase activity, IL-1[beta], IL-12p40, and IFN-[gamma]/production, and infiltration of CD[3.sup.+] T cells and macrophages in the colonic mucosa. In addition, we observed significantly lower numbers of 5-HT-expressing EC cells in the colon of MCP-1-deficient mice compared with those in wild-type mice after dinitrobenzenesulfonic acid. These results provide evidence for a critical role of MCP- 1 in the development of colonic inflammation in this model in the context of immune and enteric endocrine cells. monocyte chemottractant protein-1; dinitrobenzenesulfonic acid; CD3-positive cells; 5-hydroxytryptamine; serotonin

Peritoneal fibrosis formation is a consequence of inflammation/injury and a significant medical problem to be solved. The effects of soluble VEGF receptor type 1 (sFlt-1) gene transfer on experimental peritoneal fibrosis were examined and compared with soluble transforming growth factor-[beta] (TGF-[beta] receptor type II (sTGF[beta]RII) gene transfer. Male C57BL/6 mice were injected with 1.5 x [10.sup.8] plaque-forming unit of adenovirus encoding active TGF-[beta] (AdTGF[beta]) intraperitoneally. Some mice had been treated with sTGF[beta]RII or sFlt-1 plasmid injection into skeletal muscle with electroporation 4 days before virus administration. Mice were euthanized at day 14 after virus administration. AdTGF[beta] induced significant elevation of serum active TGF-[beta], caused significant inflammatory response [weight loss, elevation of serum amyloid-P (SAP) and IL-12, increased expression of monocyte chemoattractant protein-1 (MCP-1) mRNA], and induced marked thickening of the peritoneum and collagen deposition. Gene transfer of sFlt-1 reduced the collagen deposition ~81% in mesenteric tissue. Treatment with sFlt-1 decreased ICAM-1 and MCP-1 mRNA expression significantly. Significant negative correlation between serum sFlt-I and placental growth factor level was observed, whereas there was no significant negative correlation between sFlt-1 and VEGF. On the other hand, sTGF[beta]RII treatment enhanced the AdTGF[beta] induced inflammation (significant elevation of SAP, TNF-[alpha], and IL-12 levels and upregulation of ICAM-1 and MCP-1 mRNA expressions) and failed to prevent collagen deposition. These observations indicate that sFIt-I gene transfer might be of therapeutic benefit in peritoneal fibrosis. inflammation; adhesion; placental growth factor; monocyte chemoatractant protein-1; anti-inflammatory cytokine

In our previous studies, we demonstrated that during Trichinella spiralis infection, T helper (Th) 2 cells contribute to the development of intestinal muscle hypercontractility and worm expulsion from the gut via STAT6. In addition, we have linked the altered muscle contractility to the eviction of the parasite and thereby to the host defense. However, the initial events linking infection to the development of muscle hypercontractility are poorly understood. In this study, we examined the contribution of CD40-CD40 ligand (CD40L) interaction in the development of intestinal muscle hypercontractility, in monocyte chemoattractant protein-1 (MCP-1) production, and in the Th2 response in CD40 ligand-deficient (CD40L -/-) mice infected with T. spiralis. Expulsion of intestinal worms was substantially delayed in CD40L -/- mice compared with the wild-type mice after T. spiralis infection. Consistent with delayed worm expulsion, there was a significant attenuation of intestinal muscle contractility in CD40L -/- mice. Infected CD40L -/- mice also exhibited marked impairment in the production of MCP-1, IL-4, IL-13, IgG1, IgE, and mouse mucosal MCP 1 (MMCP-1), and in goblet cell response. These results demonstrate that CD40-CD40 ligand interaction plays an important role in MCP-1 production, Th2 response, intestinal muscle hypercontractility, and worm expulsion in nematode infection. The present data suggest that the early events leading to the generation of Th2 response include CD40-CD40 ligand interaction, which subsequently influences the production of Th2 cytokines, most likely via upregulation of MCP-1. CD40 ligand; monocyte chemoattractant protein-1; T helper 2 cells: muscle; Trichinella spiralis; host defense

The production and recombination phenomena of a material is revealed by discrete changes in the excess carrier density and in the corresponding spaces between excess carriers. The band-to-band transitions and deep-level taps are caused by the phenomena. The carriers are created by the bond-to-bond transition and transitions from the impurity levels to the levels of conduction. The phenomena produce an overall non-ideal behavior of the semiconductors.

Peritoneal fibrosis formation is a consequence of inflammation/injury and a significant medical problem to be solved. The effects of soluble VEGF receptor type I (sFlt-1) gene transfer on experimental peritoneal fibrosis were examined and compared with soluble transforming growth factor-β (TGF-β) receptor type II (sTGFβRII) gene transfer. Male C57BL/6 mice were injected with 1.5 × 108 plaque-forming unit of adenovirus encoding active TGF-β (AdTGFβ) intraperitoneally. Some mice had been treated with sTGFβRII or sFlt-1 plasmid injection into skeletal muscle with electroporation 4 days before virus administration. Mice were euthanized at day 14 after virus administration. AdTGFβ induced significant elevation of serum active TGF-β, caused significant inflammatory response [weight loss, elevation of serum amyloid-P (SAP) and IL-12, increased expression of monocyte chemoattractant protein-I (MCP-1) mRNA], and induced marked thickening of the peritoneum and collagen deposition. Gene transfer of sFlt-1 reduced the collagen deposition ∼81% in mesenteric tissue. Treatment with sFlt-1 decreased ICAM-1 and MCP-1 mRNA expression significantly. Significant negative correlation between serum sFlt-1 and placental growth factor level was observed, whereas there was no significant negative correlation between sFlt-1 and VEGF. On the other hand, sTGFβRII treatment enhanced the AdTGFβ-induced inflammation (significant elevation of SAP, TNF-α, and IL-12 levels and upregulation of ICAM-1 and MCP-1 mRNA expressions) and failed to prevent collagen deposition. These observations indicate that sFlt-1 gene transfer might be of therapeutic benefit in peritoneal fibrosis. [ABSTRACT FROM AUTHOR]

Information about interleukin-3 (IL-3) effects in vivo is limited compared with the in vitro effects. We found that a repetitive injection of a Iow dose of recombinant IL-3 induced protection against intestinal worms of Strongyloides ratti in C57BL/6 mice. When mice were injected i.p. with different doses of recombinant IL-3 twice a day from day -5 to day -1 and infected orally with larvae recovered from the head of infected rats on day 0, worm recovery from the small intestine was markedly reduced by a total of 104 U IL-3 or more on day 2 post-infection. The number of intestinal mucosal mast cells (MMC) was increased by the protective dose of IL-3. The IL-3 treatment, however, was ineffective in protecting mice against tissue migrating larvae, as assessed by recovery from the head. The protective effect of IL-3 on intestinal worms was observed within 6 hr post oral infection, suggesting little concern with antigen-specific immune responses. The effective dose of IL-3 treatment increased the number of MMC progenitors five times in the spleen and the mesenteric lymph nodes. An MMC-specific protease, MMCP-1, was secreted 200 times more than in controls in the intestinal lumen by the IL-3 treatment. The IL-3 treatment induced no protection or mastocytosis in mast cell-deficient W/Wv mice. These results suggest that the IL-3-induced intestinal protection against S. ratti is mediated by MMC. [ABSTRACT FROM AUTHOR]