IL-1β and TLR4 signaling are involved in the aggravated murine acute graft-versus-host disease caused by delayed bortezomib administration

The Journal of Immunology : Official Journal of the American Association of Immunologists
Yong LiangHaiyan Liu

Abstract

It was shown that the proteasome inhibitor, bortezomib, administered immediately following allogeneic bone marrow transplantation resulted in marked inhibition of acute graft-versus-host disease (aGVHD), with retention of graft-versus-tumor effects. However, continuous bortezomib administration resulted in significant acceleration of graft-versus-host disease-dependent morbidity. We carried out studies to dissect the mechanisms of aggravated aGVHD caused by delayed bortezomib administration. First, we demonstrated that IL-1β was critically involved, and the subsequent aGVHD could be alleviated by IL-1β blockade. Bortezomib treatment after dendritic cell (DC) activation resulted in drastically elevated IL-1β production, whereas bortezomib treatment before DC activation inhibited IL-1β production, suggesting that the timing of bortezomib administration significantly affected IL-1β production by DCs. We further demonstrated that delayed administration of bortezomib accelerated aGVHD through TLR4 signaling. Because the LPS levels were much lower with reduced-intensity conditioning compared with high-dose irradiation, the accelerated graft-versus-host disease-dependent morbidity with delayed bortezomib administration could be rescue...Continue Reading

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Citations

Nov 27, 2016·Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation·Ahmad Samer Al-HomsiYuxin Feng
Apr 29, 2018·The Journal of Experimental Medicine·Katherine StockstillDaniela Salvemini
Dec 27, 2018·British Journal of Haematology·Xiaoping LiXi Zhang
May 15, 2018·Frontiers in Immunology·Andrzej GórskiJan Borysowski
Aug 27, 2014·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jian GuSong Guo Zheng
May 16, 2020·Frontiers in Immunology·Stephanie Kim, Pavan Reddy
May 18, 2020·International Immunopharmacology·Miten MehtaVikram Gota
Oct 29, 2021·Journal of Biomedical Nanotechnology·Yong LiangQiyun Tang

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