Tazuko Ohishi

Anti-fibrogenic effect of an angiotensin converting enzyme inhibitor on chronic carbon tetrachloride-induced hepatic fibrosis in rats

The tissue renin-angiotensin system has recently been demonstrated to reduce fibrogenesis in various organs. However, little has been clarified regarding its role in hepatic fibrosis. The purpose of this study was to investigate the effect of angiotensin-converting enzyme inhibitors on liver fibrogenesis induced in rats by low-dose chronic carbon tetrachloride administration. We used lisinopril that is absorbed in its active form and not metabolized in the liver to avoid any influence by the administration of the chemical. Carbon tetrachloride was administered twice a week i.p. Twelve and 24 weeks after the start of treatment, expanded periportal fibrosis or portal-portal bridgings and severe fat deposition were observed in the rats treated with carbon tetrachloride alone, and these findings were significantly reduced with the simultaneous treatment with lisinopril. The hydroxyproline content of the liver was significantly lower in the lisinopril-treated group. Angiotensin II up-regulated mRNA of pro alpha (I) collagen and transforming growth factor-beta in isolated hepatic stellate cells. These results suggest that the local tissue renin-angiotensin system plays a role in rat hepatic fibrogenesis induced by chronic carbon tetrachloride administration and that hepatic fibrogenesis is significantly reduced by ACE inhibitors.

Laparoscopically assisted ileocecal resection for Crohn's disease associated with intestinal stenosis and ileovesical fistula.

We describe a 22-year-old man with Crohns ileocolitis accompanied by intestinal stenosis and ileovesical fistula in whom laparoscopically-assisted surgery was successfully performed after thorough nutritional therapy. Laparoscopic procedures are characterized by minimal access and minimal invasion, features which can contribute to the early recovery of patients who undergo surgery. It is suggested that laparoscopic (or laparoscopically-assisted) surgery after strict nutritional therapy can be effective in the treatment of patients with Crohns disease who have intestinal complications.

Th1 and Th2 cytokines differentially regulate the transformation of Kupffer cells into multinucleated giant cells but similarly enhance the Kupffer cell-induced hepatic stellate cell proliferation

To investigate the effects of T-helper cytokines on Kupffer cells (KCs), the effects of interferon-gamma (IFN-gamma; Th1 cytokine) and interleukin-4 (IL-4; Th2 cytokine) on KC morphology and their role in modulating the growth of hepatic stellate cells (HSCs) were examined. Fluorescence microscopic and electron microscopic data demonstrated that IL-4 transforms rat KCs into multinucleated giant cells (MGCs) in vitro. This transformation was inhibited by the addition of anti-ICAM-1 and anti-CD18 monoclonal antibodies. In addition, IL-4-induced KC transformation was suppressed by the presence of IFN-gamma. The formation of mouse hepatic MGCs was also demonstrated in vivo by the intraperitoneal injection of recombinant mouse IL-4. Although the presence of MGCs was found in all five out of five livers from IL-4-treated Th2-dominant BALB/c mice, but it was in only two out of five livers from IL-4-treated Th1-dominant C57BL/6 mice. In addition, fewer MGCs were found in the liver of C57BL/6 mice. In contrast, IFN-gamma treatment did not form hepatic MGCs in mice at all. The growth of HSCs in vitro was significantly increased by the addition of culture supernatant from lipopolysaccharide-stimulated rat KCs. Pretreatment of the KCs with either IFN-gamma or IL-4 further enhanced the growth stimulation. These results suggest that IFN-gamma and IL-4 affect KC morphology differently, but that both Th1 and Th2 cytokines play a similar role in the modulation of HSC growth by Kupffer cells in the presence of lipopolysaccharide.

Different response of rat Kupffer cells to lipopolysaccharide after exposure to T-helper cytokines

Abstract Effects of interleukin-4 (IL-4) and interferon-γ (IFN-γ) on rat Kupffer cell (KC) functions were investigated. Lipopolysaccharide (LPS)-stimulated KCs pretreated with IL-4 produced much more prostaglandin E 2 than those pretreated with IFN-γ. In contrast, LPS-stimulated KCs pretreated with IFN-γ produced much more tumor necrosis factor-α, and nitrate and nitrite than those pretreated with IL-4. Different morphologic changes were induced after the culture with each cytokine; transformation of KCs into multinucleated giant cells with IL-4 was especially noted. These results suggest that IFN-γ and IL-4, produced by different subsets of T-helper lymphocytes, differently induce KC into specific morphology, and change KC response to endotoxins, possibly resulting in a modulation of hepatic inflammation.