Transforming growth factor-beta signaling is enhanced following mitomycin-C treatment of islet xenograft.
Mitomycin-C (MMC) is categorized as an agent that causes genotoxic stress by triggering various intracellular signaling pathways. We have previously shown that MMC pretreatment of highly immunogenic crude islets leads to significant prolongation of graft survival in a rat-to-mouse model. In the present study, we examined whether TH1/TH2 cytokine, including the inflammatory cytokines interferon-gamma and interleukin (IL)-2, or the Th2 group, IL-4, IL-10, TNF-alpha, IL-1 beta, IL-6, GM-CSF, and transforming growth factor (TGF)-beta were up-regulated or down-regulated following MMC treatment of islets. We found changes in TGF-beta messenger RNA (mRNA) transcription as the only events among the measured cytokines. TGF-beta concentration was elevated in blebs formed under the kidney capsule, but not in the serum or ascites among animals given MMC-treated islets than in animals given untreated islets, suggesting local processes induced by MMC might inhibit xenograft rejection.
Ise
K
K
Department of Surgery, Fukushima Medical University, Fukushima, Japan.
Sato
Y
Y
Matsuyama
S
S
Gunji
T
T
Ishii
S
S
Yamashita
M
M
Kanazawa
Y
Y
Gotoh
M
M
D000818:Animals; D016207:Cytokines / Q000235:genetics*; D005786:Gene Expression Regulation; D006085:Graft Survival; D007515:Islets of Langerhans / Q000187:drug effects / Q000502:physiology; D016381:Islets of Langerhans Transplantation / Q000276:immunology / Q000502:physiology*; D051379:Mice; D016685:Mitomycin / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects*; D013370:Subrenal Capsule Assay; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000502:physiology*; D014183:Transplantation, Heterologous
D016207:Cytokines; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D016685:Mitomycin