PMID- 12911125
OWN - NLM
STAT- MEDLINE
DCOM- 20040324
LR  - 20211203
IS  - 0963-6897 (Print)
IS  - 0963-6897 (Linking)
VI  - 12
IP  - 4
DP  - 2003
TI  - Suppression of allogeneic response by viral IL-10 gene transfer.
PG  - 379-87
AB  - Th1 cell activation and cytokine production shift the balance between Th1 and 
      Th2, favoring the upregulation of proinflammatory activity that leads to 
      destruction of allogeneic hepatocytes following transplantation. Th2-type 
      cytokines. such as IL-10, have immune regulatory function. The aim of this study 
      was to determine the antirejection efficacy of allogeneic hepatocytes with 
      spheroidal shape (spheroids) genetically modified with viral IL-10 (vIL-10). 
      Allogeneic hepatocyte spheroids, transferred vIL-10 gene by using adenovirus as 
      the vector, were transplanted into the spleen of Nagase's analbuminemic rats 
      (NAR). NAR transplanted with vIL-10-transfected hepatocytes showed an abrupt rise 
      in serum albumin levels that peaked on day 7 and remained at high levels up to 
      day 21 after transplantation. The peak level of albumin on day 7 in 
      vIL-10-transfected NAR was eminently higher than that in nontransfected NAR. 
      Histopathological analysis revealed that in nontransfected NAR hepatocyte 
      spheroids were more or less rejected on day 4, and, in contrast, 
      vIL-10-transfected spheroids were still not rejected on day 14. This protective 
      effect correlated with sustained high vIL-10 level in the splenic vein in NAR 
      transplanted with vIL-10-transfected hepatocyte spheroids, suggesting that vIL-10 
      secreted from the transplanted hepatocytes induced an active suppression of 
      allogeneic response. This study provides evidence to support the possibility of 
      using vIL-10 gene therapy to prevent allogeneic response in hepatocyte 
      transplantation.
FAU - Fujisawa, Kenji
AU  - Fujisawa K
AD  - Department of Gastroenterological Surgery and Transplant, Okayama University 
      Graduate School of Medicine and Dentistry, Okayama city, 700-8558 Japan.
FAU - Saito, Shinya
AU  - Saito S
FAU - Okada, Yutaka
AU  - Okada Y
FAU - Fujiwara, Toshiyosi
AU  - Fujiwara T
FAU - Yagi, Takahito
AU  - Yagi T
FAU - Iwagaki, Hiromi
AU  - Iwagaki H
FAU - Tanaka, Noriaki
AU  - Tanaka N
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Cell Transplant
JT  - Cell transplantation
JID - 9208854
RN  - 0 (Galactosides)
RN  - 0 (Indoles)
RN  - 0 (Serum Albumin)
RN  - 130068-27-8 (Interleukin-10)
RN  - V595OG374W (5-bromo-4-chloro-3-indolyl beta-galactoside)
SB  - IM
MH  - Adenoviridae/genetics
MH  - Animals
MH  - Galactosides/genetics
MH  - Gene Transfer Techniques
MH  - Genes, Reporter/genetics
MH  - Genetic Vectors/genetics/immunology
MH  - Graft Rejection/*prevention & control
MH  - Hepatocytes/*immunology/metabolism/*transplantation
MH  - Immunosuppression Therapy/*methods
MH  - Indoles
MH  - Interleukin-10/biosynthesis/*genetics/therapeutic use
MH  - Lymphocyte Activation/genetics/immunology
MH  - Male
MH  - Rats
MH  - Rats, Inbred Strains
MH  - Serum Albumin/biosynthesis/metabolism
MH  - Spheroids, Cellular/immunology/transplantation
MH  - Th1 Cells/immunology
MH  - Th2 Cells/immunology
MH  - Transplantation Tolerance/*immunology
MH  - Transplantation, Homologous/immunology/methods
EDAT- 2003/08/13 05:00
MHDA- 2004/03/25 05:00
CRDT- 2003/08/13 05:00
PHST- 2003/08/13 05:00 [pubmed]
PHST- 2004/03/25 05:00 [medline]
PHST- 2003/08/13 05:00 [entrez]
AID - 10.3727/000000003108746920 [doi]
PST - ppublish
SO  - Cell Transplant. 2003;12(4):379-87. doi: 10.3727/000000003108746920.