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Background: Portal hypertensive gastropathy is an abnormal circulatory state in gastric mucosa with vascular dilatation due to portal hypertension. The aim of the present study was to evaluate expression of endothelin receptors and their roles in the portal hypertensive gastric mucosa. Methods: Portal hypertensive rats were generated by staged portal vein occlusion. Expression of endothelin-A receptor and endothelin-B receptor mRNA was examined by reverse transcriptase–polymerase chain reaction, and protein were examined by immunohistochemistry. The changes of mucosal microcirculation by endothelin receptor antagonists were measured with in vivo microscope. Results: Expression of endothelin-A receptor mRNA was increased significantly in portal hypertensive rats in comparison with sham-operated control rats (P < 0.05). There was no significant difference between the two groups in endothelin-B receptor mRNA expression. Vessels of the gastric mucosa were dilated, and intravessel blood flow was increased significantly in the portal hypertensive group (P < 0.05). Diameters of mucosal vessels and blood flow were increased significantly by endothelin-A receptor antagonist (BQ-485) in the portal hypertensive rats. Endothelin-B receptor antagonist (IRL-1038) had no significant effect on mucosal microcirculation. Conclusion: These data suggest that increased expression of endothelin-A receptor in the portal hypertensive gastric mucosa may be related to the regulation of gastric microcirculation.

Background and Aims: Portal hypertensive (PHT) gastropathy results in an increased susceptibility to damage. Adaptive cytoprotection against ethanol-induced damage is impaired in the gastric mucosa of rats with portal hypertension. Excessive nitric oxide (NO) production occurs in portal hypertension and is mediated in part via heat-shock protein (Hsp)90 production. The aim of this study was to investigate the relation between adaptive cytoprotection after exposure to ethanol and gastric expression of Hsp90 in PHT rats. Methods: Portal hypertension was induced in rats by staged portal vein occlusion. Adaptive cytoprotection to 70% ethanol was evaluated by assessing the injury index of the gastric mucosa with or without pretreatment with 10% ethanol. Expression of Hsp90 mRNA was evaluated by real-time polymerase chain reaction, and expression of Hsp90 protein was evaluated by western blotting. The effect of Hsp90 inhibition in PHT rats was evaluated by administration of geldanamycin. Results: Gastric Hsp90 mRNA expression in PHT rats was significantly less than that in sham-operated (SO) controls. However, after 10% ethanol pretreatment, Hsp90 mRNA expression was significantly greater in PHT rats than in SO controls. In PHT rats, gastric Hsp90 protein expression after 10% ethanol pretreatment was significantly greater than that without the pretreatment. However, the pretreatment had no effect on the injury index compared to SO rats. Administration of geldanamycin prior to 10% ethanol pretreatment significantly decreased the injury index in response to 70% ethanol in the PHT rats. Conclusions: These results show that 10% ethanol pretreatment markedly increases gastric Hsp90 expression in PHT rats. Excessive production of Hsp90 may contribute impaired adaptive cytoprotection.

Background The infiltration of lymphocytes in tumor tissue has been associated with a good prognosis for patients with hepatocellular carcinoma (HCC). The purpose of the present study was to estimate the correlation between mRNA expression of chemokines and tumor-infiltrating lymphocytes in HCC. Methods A total of 44 HCC were examined. Immunohistochemical staining was performed using antibodies to CD4, CD8, CD68, and L-26. The mRNA expression of each chemokine was investigated: regulated upon activation normal T-cell expressed and secreted (RANTES), interleukin-8 (IL-8), epithelial-derived neutrophil attractant-78 (ENA78), interferon-inducible protein-10 (IP-10), monokine induced by interferon-gamma (Mig), and interferon-gamma in HCC were quantified via a real-time polymerase chain reaction assay. Chemokine proteins of Mig and IP-10 were examined by immunohistochemistry. Results The mean number of infiltrating lymphocytes in HCC was 136.9 +/- 32.9/0.25 mm2. Of these infiltrating lymphocytes, CD8-positive T lymphocytes were those predominantly seen around the tumor cells. The mean mRNA expression (copies/10(3) glyceraldehyde-3-phosphate dehydrogenase [GAPDH] mRNA) of the following chemokines was determined to be follows: 3.0 +/- 1.9 copies/10(3) GAPDH mRNA, RANTES; 9.2 +/- 4.9 copies/10(3) GAPDH mRNA, IL-8; 44.6 +/- 24.4 copies/10(3) GAPDH mRNA, ENA78; 215.7 +/- 93.9 copies/10(3) GAPDH mRNA, IP-10; 77.3 +/- 38.5 copies/10(3) GAPDH mRNA, Mig; and 1.7 +/- 0.4 copies/10(3) GAPDH mRNA, interferon-gamma. Significant close correlations were observed between the number of infiltrating lymphocytes in these HCC and the expression of Mig and IP-10 mRNA. In the immunostaining, expression of Mig and IP-10 proteins was found only in the HCC cells in the high-infiltration group. Conclusions Some chemokines induced by interferon-gamma, such as Mig and IP-10, may promote lymphocyte recruitment to HCC and may thus play important roles in cancer immunology.