| Autor: |
Perez, Richard, Stevenson, Frazier, Johnson, Jeremy, Morgan, Murray, Erickson, Kent, Hubbard, Neil E., Morand, Larry, Rudich, Steven, Katznelson, Steven, German, J.Bruce |
| Zdroj: |
Journal of Surgical Research; July 1998, Vol. 78 Issue: 1 p1-6, 6p |
| Abstrakt: |
The immunosuppressive effect of portal venous blood transfusions in organ transplantation has been well established and may be mediated by increased Kupffer cell production of the immunosuppressive arachidonic acid metabolite prostaglandin E2(PGE2). In this study, butyrate, a short-chain fatty acid known to enhance gene transcription, is hypothesized to enhance Kupffer cell PGE2production by altering cyclooxygenase or phospholipase A2(PLA2) activity, thus augmenting the immunosuppressive effect of portal venous transfusion. Lewis rats were given a portal venous transfusion of Wistar-Firth blood or saline 1 h prior to Kupffer cell harvest. Thein vitroeffects of butyrate on Kupffer cell PGE2production, cyclooxygenase, and PLA2activity were assessed. Kupffer cell tumor necrosis factor-alpha (TNFα) production was also assessed due to its sensitivity to PGE2and its proinflamatory effects. Kupffer cells from portally transfused animals produced significantly more PGE2than saline-transfused controls. Addition of butyrate to the culture medium further increased PGE2production by as much as sevenfold in Kupffer cells of portally transfused animals. Other short-chain fatty acids, propionate and hexanoate, did not increase PGE2production. Butyrate added to Kupffer cells from transfused animals slightly upregulated inducible cyclooxygenase (COX-2) mRNA levels as measured by both Northern blot and reverse-transcriptase polymerase chain reaction and increased PLA2activity fivefold as measured by Western blot. Kupffer cell immune function was also affected byin vitrobutyrate treatment with a significant decrease in the production of TNFα. Thus, butyrate may be a useful immunoregulatory agent in organ transplantation protocols which seek to enhance transcription of immunosuppressive molecules. |
| Databáze: |
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