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Experimental Biology and Medicine 231:444-455 (2006)
© 2006 Society for Experimental Biology and Medicine


ORIGINAL RESEARCH ARTICLE

Effects of Scutellaria baicalensis Georgi on Macrophage-Hepatocyte Interaction Through Cytokines Related to Growth Control of Murine Hepatocytes

Jir-You Wang*, Han-Ning Chuang*, Jen-Hwey Chiu*,{dagger},{ddagger},1, Shu-Ling Fu*, Tung-Hu Tsai*,§, Ann-Ping Tsou||, Cheng-Po Hu, Chin-Wen Chi, Sheau-Farn Yeh#, Wing-Yiu Lui{dagger}, Chew-Wun Wu{dagger} and Chen-Kung Chou

* Institute of Traditional Medicine, School of Medicine, National Yang-Ming University, Taipei, 112, Taiwan, Republic of China; {dagger} Division of General Surgery, Department of Surgery, Veterans General Hospital, Taipei, Taiwan, Republic of China; {ddagger} Cheng-Hsiung Rehabilitation Medical Center; § National Research Institute of Chinese Medicine; || Institute of Biotechnology in Medicine, National Yang-Ming University, Taipei, 112, Taiwan, Republic of China; Medical Research and Education, Veterans General Hospital, Taipei, Taiwan, Republic of China; and # Institute of Biochemistry, National Yang-Ming University, Taipei, 112, Taiwan, Republic of China

To whom requests for reprints should be addressed at 1 Institute of Traditional Medicine, School of Medicine, National Yang-Ming University, 155, Sec. 2, Li-Nong Street, Peitou, Taipei, 112, Taiwan, R.O.C. E-mail: chiujh{at}mailsrv.ym.edu.tw

The aim of this study is to elucidate the effects of Scutellaria baicalensis Georgi (SbG) extract and its constituents on macrophage-hepatocyte interaction in primary cultures. By using trans-well primary Kupffer cell culture or conditioned medium (CM) from murine macrophage RAW264.7 cell line (RAW cells), effects of SbG on hepatocyte growth were evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide and trypan blue exclusion assay. Cytokine production, antibody-neutralization studies, and molecular mechanisms of transforming growth factor (TGF)-ß1 gene expression were elucidated on SbG-treated RAW264.7 cells. In addition, recombinant human TGF-ß1 (r-human TGF-ß1) was added to elucidate the mechanisms of SbG effects on cultured hepatocytes. Immunohistochemistry using anti–NF-{kappa}B antibody was used to determine the possible signal transduction pathways in primary hepatocyte culture. The results showed that SbG stimulated the proliferation of cultured hepatocytes, possibly through NF-{kappa}B, but not of Toll-like receptor 4 activation; whereas SbG-RAW-CM and SbG in trans-well significantly suppressed the proliferation of hepatocytes. Antibody-neutralization studies revealed that TGF-ß1 was the main antimitotic cytokine in SbG-treated RAW cells CM. The growth stimulation effect of SbG on cultured hepatocytes was inhibited by exogenous administration of r-human TGF-ß1. Furthermore, SbG induced NF-kB translocation into the nuclei of cultured cells. In the RAW264.7 line, SbG and baicalin stimulated TGF-ß1 gene expression via NF-{kappa}B and protein kinase C activation. We conclude that SbG stimulates hepatocyte growth via activation of the NF-{kappa}B pathway and induces TGF-ß1 gene expression through the Kupffer cell–hepatocyte interaction, which subsequently results in the inhibition of SbG-stimulated hepatocyte growth.

Key Words: liver regeneration • Scutellaria baicalensis Georgi • interleukin-6 (IL-6) • cDNA microarray • macrophage




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