Activin inhibition limits early innate immune response in rat kidney allografts-a pilot study

作者：Palin Niina K^*; Savikko Johanna; Pasternack Arja; Rintala Jukka M; Kalra Bhanu; Mistry Shivani; Kumar Ajay; Roth Marie Paule; Helin Heikki; Ritvos Olli

来源：Transplant International, 2017, 30(1): 96-107.

DOI：10.1111/tri.12876

• activin
• innate immunity
• ischemia-reperfusion injury
• kidney transplantation
• transforming growth factor-beta

Activins are members of the transforming growth factor-beta (TGF-beta) superfamily of cytokines. They play critical roles in the onset of acute and chronic inflammatory responses. The aim of this study was to investigate how activin inhibition affects acute kidney injury and inflammation after transplantation. The study was carried out in kidney transplantation and renal ischemia-reperfusion models in the rat. Soluble activin type 2 receptor (sActRIIB-Fc) was used to inhibit activin signaling. Transplantation groups were as follows: (i) cyclosporine A (CsA) (ii) CsA + sActRIIB-Fc, (iii) CsA+ inactive protein control Fc-G1. IRI groups were as follows: (i) no treatment, (ii) sActRIIB-Fc. Serum activin B concentration was significantly elevated after transplantation and IRI, whereas activin A was produced locally in renal allografts. Activin inhibition efficiently limited neutrophil, macrophage, and dendritic cell infiltration to the allografts measured 72 h after transplantation. In addition, sActRIIB-Fc treatment modulated serum cytokine response after transplantation and reduced the early accumulation of fibroblasts in the graft interstitium. In conclusion activin inhibition reduces the innate immune response early after renal transplantation in the rat. It also limits the accumulation of fibroblasts in the graft suggesting that activins may be involved in the fibrogenic signaling already early after kidney transplantation.

• 出版日期2017-1