Participation of contrasting changes in IL-10 and IL-12 production in the reduction of Th1-predominance by Hachimi-jio-gan in autoimmune MRL/MP-lpr/lpr mice.
Hachimi-jio-gan (Chinese name: Ba-Wei-Di-Huang-Wan, HMG), a traditional Japanese herbal medicine, has been used for disorders accompanying aging. Our previous studies suggested that HMG ameliorated Thl-predominant autoimmune diseases in MRL/lpr mice through inhibition of IL-12 production. In the present study, the oral administration of HMG down-regulated phosphorylated STAT4 and up-regulated phosphorylated STAT6 in CD4 T cells. In the T cells, IL-12Rbeta1 and IL-12Rbeta2 mRNA expression levels were suppressed. In antigen-presenting cells (CD45R- MHC class II+ cells) which control Th1 and Th2 immune responses, the total cell number and the percentage of cells expressing co-stimulatory molecules decreased in the HMG-treated group. In addition, the levels of IL-12 and 18 mRNA expression increased and conversely, IL-10 mRNA expression decreased. Further, the production of IL-10 was up-regulated and that of IL-12 was down-regulated by HMG in the presence of anti-CD40 antibody. These results suggest that the opposite effects on IL-10 production and, IL-12 or IL-18 production in antigen-presenting cells of oral administration of HMG are due a decline in IL-12R expression, and consequently, amelioration of MRL/lpr autoimmune diseases occurs through the suppression of Th1 predominance via STAT4/STAT6 signaling.
Furuya
Yuriko
Y
Department of Pharmacology, Kanebo Kampo (Traditional Japanese Medicine) & Healthcare Research Laboratories, Takaoka, Japan.
Kawakita
Takuya
T
Nomoto
Kikuo
K
D000284:Administration, Oral; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism; D001327:Autoimmune Diseases / Q000188:drug therapy / Q000235:genetics / Q000276:immunology*; D015153:Blotting, Western; D004195:Disease Models, Animal; D015536:Down-Regulation; D004365:Drugs, Chinese Herbal / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D005434:Flow Cytometry; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000276:immunology; D018664:Interleukin-12 / Q000096:biosynthesis* / Q000276:immunology; D020835:Medicine, Kampo; D051379:Mice; D019463:Mice, Inbred MRL lpr; D008517:Phytotherapy; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000187:drug effects / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism; D015854:Up-Regulation
D004365:Drugs, Chinese Herbal; D016753:Interleukin-10; D018664:Interleukin-12