Suppressive effect of a traditional Japanese medicine, Hachimi-jio-gan (Ba-Wei-Di-Huang-Wan), on the hyperresponsiveness to IL-18 in autoimmune MRL/MPJ-lpr/lpr mice.
Oral administration of Hachimi-jio-gan (HMG, Ba-Wei-Di-Huang-Wan), a traditional Japanese herbal medicine, for several weeks, ameliorates some autoimmune symptoms of MRL/lpr mice. In the short time treatment for 9 days, hyperresponsiveness of mesenteric lymph node (MLN) cells to interleukin (IL)-18 manifested by the proliferation or the production of interferon (IFN)-gamma was significantly suppressed. Additionally, the treatment with HMG suppressed the expressions of IL-18Ralpha and IL-18Rbeta mRNA in CD45R(-) T cells, and also the expression of IL-18Ralpha mRNA in unpurified whole cells. Although the short treatment with HMG had no effect on the mRNA expressions of IL-10, IL-12 and IL-18, or the phosphorelated signal transducer and activator transcription (STAT)4 protein level in CD45R(-) MLN cells, the IL-4 mRNA expression or the phosphorelated STAT6 protein level were up-regulated by HMG, and the IL-4 mRNA up-regulation was clearer in whole cells than CD45R(-) cells. Furthermore, the treatment with HMG promoted the mRNA expression of invariant Valpha14 TCR that is uniquely expressed on NKT cells. Valpha14 NKT cells can produce large amount of IL-4 and play a crucial role in controlling the development of MRL/lpr mouse autoimmune disease. Therefore, these results suggested that HMG reduced the hyperresponsiveness of MRL/lpr mouse MLN cells to IL-18 through the reduction of IL-18Rs caused by Valpha14 NKT cell-produced IL-4, and consequently HMG suppressed the development of MRL/lpr autoimmune diseases.
Furuya
Yuriko
Y
Department of Clinical Development and Pharmacology, Kanebo Kampo and Healthcare Research Laboratories, 3-1, Kanebo-machi, Takaoka 933-0856, Japan. yuri_funya@yahoo.co.jp
Kawakita
Takuya
T
Nomoto
Kikuo
K
D000818:Animals; D001327:Autoimmune Diseases / Q000235:genetics / Q000503:physiopathology*; D015153:Blotting, Western; D002469:Cell Separation; D016207:Cytokines / Q000096:biosynthesis; D004268:DNA-Binding Proteins / Q000096:biosynthesis; D003864:Depression, Chemical; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D005260:Female; D005434:Flow Cytometry; D007371:Interferon-gamma / Q000378:metabolism; D020382:Interleukin-18 / Q000502:physiology*; D017493:Leukocyte Common Antigens / Q000096:biosynthesis / Q000235:genetics; D008198:Lymph Nodes / Q000166:cytology / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D019463:Mice, Inbred MRL lpr; D010766:Phosphorylation; D012333:RNA, Messenger / Q000096:biosynthesis; D018123:Receptors, Interleukin / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050797:STAT4 Transcription Factor; D050800:STAT6 Transcription Factor; D015534:Trans-Activators / Q000096:biosynthesis
D016207:Cytokines; D004268:DNA-Binding Proteins; D004365:Drugs, Chinese Herbal; D020382:Interleukin-18; D012333:RNA, Messenger; D018123:Receptors, Interleukin; D050797:STAT4 Transcription Factor; D050800:STAT6 Transcription Factor; C494091:Stat4 protein, mouse; C494100:Stat6 protein, mouse; D015534:Trans-Activators; C054591:hachimijiogan; D007371:Interferon-gamma; D017493:Leukocyte Common Antigens