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Suppressor of cytok...
Suppressor of cytokine signalling-3 expression inhibits cytokine-mediated destruction of primary mouse and rat pancreatic islets and delays allograft rejection
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Rønn, SG (författare)
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- Börjesson, A (författare)
- Uppsala universitet,Institutionen för medicinsk cellbiologi
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Bruun, C (författare)
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Heding, PE (författare)
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Frobøse, H (författare)
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Mandrup-Poulsen, T (författare)
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Karlsen, AE (författare)
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Rasschaert, J (författare)
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- Sandler, S (författare)
- Uppsala universitet,Institutionen för medicinsk cellbiologi
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Billestrup, N (författare)
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(creator_code:org_t)
- 2008-07-22
- 2008
- Engelska.
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 51:10, s. 1873-1882
- Relaterad länk:
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https://link.springe...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Aims/hypothesis The pro-inflammatory cytokines IL-1 and IFN gamma are critical molecules in immune-mediated beta cell destruction leading to type 1 diabetes mellitus. Suppressor of cytokine signalling (SOCS)-3 inhibits the cytokine-mediated destruction of insulinoma-1 cells. Here we investigate the effect of SOCS3 in primary rodent beta cells and diabetic animal models. Methods Using mice with beta cell-specific Socs3 expression and a Socs3-encoding adenovirus construct, we characterised the protective effect of SOCS3 in mouse and rat islets subjected to cytokine stimulation. In transplantation studies of NOD mice and alloxan-treated mice the survival of Socs3 transgenic islets was investigated. Results Socs3 transgenic islets showed significant resistance to cytokine-induced apoptosis and impaired insulin release. Neither glucose-stimulated insulin release, insulin content or glucose oxidation were affected by SOCS3. Rat islet cultures transduced with Socs3-adenovirus displayed reduced cytokine-induced nitric oxide and apoptosis associated with inhibition of the IL-1-induced nuclear factor-kappa B and mitogen-activated protein kinase (MAPK) pathways. Transplanted Socs3 transgenic islets were not protected in diabetic NOD mice, but showed a prolonged graft survival when transplanted into diabetic allogenic BALB/c mice. Conclusions/interpretation SOCS3 inhibits IL-1-induced signalling through the nuclear factor-kappa B and MAPK pathways and apoptosis induced by cytokines in primary beta cells. Moreover, Socs3 transgenic islets are protected in an allogenic transplantation model. SOCS3 may represent a target for pharmacological or genetic engineering in islet transplantation for treatment of type 1 diabetes mellitus.
Nyckelord
- apoptosis
- autoimmunity
- diabetes
- IFN gamma
- IL-1
- inflammation; signalling
- SOCS
- suppressor of cytokine signalling
- MEDICINE
- MEDICIN
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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Till lärosätets databas
- Av författaren/redakt...
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Rønn, SG
-
Börjesson, A
-
Bruun, C
-
Heding, PE
-
Frobøse, H
-
Mandrup-Poulsen, ...
-
visa fler...
-
Karlsen, AE
-
Rasschaert, J
-
Sandler, S
-
Billestrup, N
-
visa färre...
- Artiklar i publikationen
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Diabetologia
- Av lärosätet
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Uppsala universitet