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- Hernebring, Malin, 1978, et al.
(författare)
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Removal of damaged proteins during ES cell fate specification requires the proteasome activator PA28
- 2013
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322 .- 2045-2322. ; 3:3, s. artikel nr 1381-
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Tidskriftsartikel (refereegranskat)abstract
- In embryonic stem cells, removal of oxidatively damaged proteins is triggered upon the first signs of cell fate specification but the underlying mechanism is not known. Here, we report that this phase of differentiation encompasses an unexpected induction of genes encoding the proteasome activator PA28 alpha beta (11S), subunits of the immunoproteasome (20Si), and the 20Si regulator TNF alpha. This induction is accompanied by assembly of mature PA28-20S(i) proteasomes and elevated proteasome activity. Inhibiting accumulation of PA28 alpha using miRNA counteracted the removal of damaged proteins demonstrating that PA28 alpha beta has a hitherto unidentified role required for resetting the levels of protein damage at the transition from self-renewal to cell differentiation.
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| 2. |
- Ingelsten, Madeleine, 1978, et al.
(författare)
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Rapid Increase of Interleukin-10 Plasma Levels After Combined Auxiliary Liver-Kidney Transplantation in Presensitized Patients
- 2014
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Ingår i: Transplantation. - : Ovid Technologies (Wolters Kluwer Health). - 0041-1337. ; 98:2, s. 208-215
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Tidskriftsartikel (refereegranskat)abstract
- Background. After transplantation, donor dendritic cells (DCs) in the grafted organ are activated by an ischemia/reperfusion-induced inflammatory process that induces their migration to the recipient's secondary lymphoid tissues. The subsequent interaction between migrated and mature donor DCs, recipient T cells, and natural killer (NK) cells is proposed to be crucial in directing host immune reactions toward allograft rejection. A liver transplant is less prone to induce rejection compared with most other solid organ transplants, and simultaneous transplantation of liver and kidney is known to improve the clinical outcome of kidney transplantation. Methods and Results. Here we show that liver as well as combined auxiliary liver-kidney transplantation in patients induces a rapid increase in plasma interleukin-10 (IL-10) to levels that are significantly higher than those seen after standard kidney transplantation. Addition of IL-10 during in vitro maturation of human monocyte-derived DCs with ischemia/reperfusion-associated factors was found to affect phenotypic DC maturation significantly. Addition of IL-10 inhibited DC production of the NK cell- and T cell-recruiting chemokines CXCL9, CXCL10 and CXCL11. Conclusion. Our findings indicate that liver transplantation induces a substantial systemic release of IL-10, which may inhibit T cell- and NK cell- mediated rejection processes toward the transplanted liver and concurrently transplanted kidney.
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