Hepatitis: Saiki I

Saiki I, Yamazaki M, Matsumoto K. · Division of Pathogenic Biochemistry, Institute of Natural medicine, University of Toyama, Japan. · Yakugaku Zasshi. · Pubmed #19336991 links to  free full text

Abstract: The Core University Program provides a framework for international cooperative research in specifically designated fields and topics, centering around a core university in Japan and its counterpart university in other countries. In this program, individual scientists in the affiliated countries carry out cooperative research projects with sharply focused topics and explicitly delineated goals under leadership of the core universities. The Core University Program which we introduce here has been renewed since 2001 under the support of both the Japan Society for the Promotion of Science (JSPS) and the National Research Council of Thailand (NRCT). Our program aims to conduct cooperative researches particularly focusing on Natural Medicine in the field of Pharmaceutical Sciences. Institute of Natural Medicine at University of Toyama (Japan), Faculty of Pharmaceutical Sciences at Chulalongkorn University (Thailand), and Chulabhorn Research Institute (Thailand) have been taking part in this JSPS-NRCT Core University Program as core universities. The Program is also supported by the 20 institution members in both countries. This program is running the five research subject under a key word of natural medicine which are related to i) age-related diseases, ii) allergy and cancer, iii) hepatitis and infectious diseases, iv) structure, synthesis, and bioactivity of natural medicines, and v) molecular biology of Thai medicinal plant components and database assembling of Thai medicinal plants. The program also encourages university members to strengthen related research activities, to share advanced academic and scientific knowledge on natural medicines.

Sawada S, Murakami K, Murata J, Tsukada K, Saiki I. · Department of Pathogenic Biochemistry, Institute of Natural Medicine, Toyama, Japan. · Int J Oncol. · Pubmed #11408924 No free full text.

Abstract: The liver undergoes pathogenic changes such as hepatitis, fibrosis and cirrhosis under continuous stimulation by hepatitis virus or alcohol intake, leading to the development of hepatocellular carcinoma. The metastatic potential of HCC can be positively or negatively regulated by pathogenic alterations of liver. We investigated whether the metastatic abilities of HCC after orthotopic implantation can be influenced in the fibrotic liver by continuous injection of carbon-tetrachloride (CCl4) for seven weeks. The incidence of lung metastasis after orthotopic implantation of murine HCC (CBO140C12) fragments into CCl4-treated livers was higher than into normal livers. The amount of mRNA for MMP-2 increased in the CCl4-treated livers as compared with normal livers, and CBO140C12 cells constitutively expressed mRNA for MT1-MMP in early amplification cycles by RT-PCR. In addition, we found that the culture of CBO140C12 cells on the substrates pre-coated with ECM components increased the expression of MMP-2 mRNA. Thus, enhanced incidence of lung metastasis in the fibrotic liver might be partly due to: i) over-expression of MMP-2 in the fibrotic liver in cooperation with MT1-MMP on the CBO140C12 cell surface, ii) over-expression of MMP-2 in CBO140C12 cells, possibly mediated by the interaction of tumor cells (surface integrins) with accumulated ECM in the fibrotic liver. This is the first report showing that increase of MMP-2 in the fibrotic liver can influence the metastatic potential of HCC cells.

Xu Q, Cao J, Wu F, Hayakawa Y, Saiki I, Koda A. · Department of Pharmacology for Chinese Materia Medica, China Pharmaceutical University, Nanjing. · Liver. · Pubmed #10661680 No free full text.

Abstract: AIMS/BACKGROUND: We have previously reported that a new model of liver injury induced in mice by delayed-type hypersensitivity (DTH) to picryl chloride (PCl) mimicks the pathogenesis of human hepatitis. This liver injury is mediated by CD4+ T cells. The interaction between lymphocyte function associated antigen 1 (LFA-1) and intercellular adhesion molecule 1 (ICAM-1) is an essential process for hepatocyte (HC) damage. The present study was undertaken to reveal the role of Th1 and Th2-like cytokines in regulating the liver injury. METHODS: The kinetics of cytokine production were examined by ELISA and RT-PCR after the elicitation of liver injury for both serum protein and liver mRNA expression, respectively. A co-culture assay between liver nonparenchymal cells (NPC) and HC was conducted to evaluate the cytokine regulation on the cell-cell interaction. Expression of LFA-1 on NPC and ICAM-1 on HC were examined by FACScan and ELISA, respectively. RESULTS: Serum IL-2 and IFN-gamma showed a peak production at 6 and 12 h, while IL-5 and IL-4 reached their maximum levels at 18 and 24 h after induction of liver injury, respectively. Liver mRNA expression of IFN-gamma and IL-4 had a similar time course to their corresponding products. Both recombinant murine IFN-gamma and IL-2 triggered the hepatotoxicity of NPC or spleen cells at 0 h. In this case, an increased expression of both LFA-1 on NPC and ICAM-1 on HC was also observed. In contrast, IL-4 and IL-5 completely abolished the hepatotoxicity of NPC at 12 h without influencing the adhesion molecules. CONCLUSION: Th1 and Th2 may be involved in regulating liver injury. Th1/Th2 balance may critically contribute to the production of the liver injury or recovery from it.