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- HEDGES, S., et al.
(författare)
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Cyclosporin A does not Inhibit IL‐lα‐Induced Epithelial Cell IL‐6 Secretion
- 1993
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Ingår i: Scandinavian Journal of Immunology. - : Wiley. - 0300-9475 .- 1365-3083. ; 37:5, s. 581-586
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Tidskriftsartikel (refereegranskat)abstract
- Trauma and infection activated a murine mucosal IL‐6 response in different ways: the IL‐6 response to bacteria was sensitive to Cyclosporin A (CsA); the IL‐6 response to trauma was not. The aim of the present study was to identify possible activators of the CsA‐insensitive IL‐6 secretion at the epithelial cell level. Two human epithelial cell lines from the kidney (A498) and bladder (J82) were exposed to Escherichia coli Hu734, interleukin‐lα (IL‐lα) and tumour necrosis factor a (TNF‐α). The E. coli strain had been used for the in vivo experiments which led to this study, and IL‐lα and TNF‐α were likely to be released during infections and trauma. The secretion of IL‐6 into the supernatants was compared between cells stimulated in the presence or absence of CsA. E. coli Hu734, IL‐lα and TNF‐α stimulated an IL‐6 response in the two epithelial cell lines. The IL‐lα‐induced IL‐6 response was rapid, and the secreted IL‐6 levels were significantly higher than those induced by E. coli Hu734 or TNF‐α. The IL‐6 response to IL‐ lα was insensitive to CsA. By contrast, the IL‐6 response to E. coli Hu734 and TNF‐α was inhibited by CsA. These results demonstrated that the inhibitory effect of CsA depends on the stimulus triggering the IL‐6 response. IL‐lα may play a role in the induction of trauma‐associated CsA‐insensitive IL‐6 secretion.
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| 2. |
- Jacobson, S., et al.
(författare)
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Alloreactivity but Failure to Reject Human Islet Transplants by Humanized Balb/c/Rag2(-/-)gc(-/-) Mice
- 2010
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Ingår i: Scandinavian Journal of Immunology. - : Wiley. - 0300-9475 .- 1365-3083. ; 71:2, s. 83-90
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Tidskriftsartikel (refereegranskat)abstract
- A human islet transplant can cure patients with type 1 diabetes. A drawback of islet transplantation is the life-long immunosuppressive medication, often associated with severe side effects. Moreover, in spite of the immunosuppressive therapy, islets are lost in the majority of transplanted patients over time. An improved small animal model for studies on human islet allograft rejection mechanisms and the development of new measures for its prevention is clearly warranted. Here, we evaluated the potential of Balb/cRag2(-/-)gamma c(-/-) mice carrying a human-like immune system (so-called humanized mice) as a tool for studies on the rejection of transplanted human islets. Human T cells from Balb/cRag2(-/-)gamma c(-/-) mice, which as neonates had been transplanted with CD34(+) human cord blood haematopoietic stem cells (HIS mice), proliferated in response to allogeneic human dendritic cells, but failed to reject a human islet allograft transplanted to the renal subcapsular space as assessed by immunohistochemistry and analysis of human serum C-peptide levels. Histological analysis revealed that few if any T cells had migrated to the grafted tissue. These observations question the usefulness of the HIS mouse model for studies on human islet allograft rejection mechanisms and highlight the need for further improvements.
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