title: Activin inhibition limits early innate immune response in rat kidney allografts-a pilot study.
abstract: Activins are members of the transforming growth factor-beta (TGF-β) 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.
authors.affiliation: Kidney Transplant Research Group, Transplantation Laboratory, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
authors.forename: Niina K
authors.initials: NK
authors.lastname: Palin
authors.affiliation: Kidney Transplant Research Group, Transplantation Laboratory, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.|Transplantation and Liver Surgery Unit, Helsinki University Hospital, Helsinki, Finland.
authors.forename: Johanna
authors.initials: J
authors.lastname: Savikko
authors.affiliation: Department of Bacteriology and Immunology and Department of Physiology, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
authors.forename: Arja
authors.initials: A
authors.lastname: Pasternack
authors.affiliation: Kidney Transplant Research Group, Transplantation Laboratory, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
authors.forename: Jukka M
authors.initials: JM
authors.lastname: Rintala
authors.affiliation: ANSH Labs Inc, Webster, TX, USA.
authors.forename: Bhanu
authors.initials: B
authors.lastname: Kalra
authors.affiliation: ANSH Labs Inc, Webster, TX, USA.
authors.forename: Shivani
authors.initials: S
authors.lastname: Mistry
authors.affiliation: ANSH Labs Inc, Webster, TX, USA.
authors.forename: Ajay
authors.initials: A
authors.lastname: Kumar
authors.affiliation: Inserm U1043, CHU Purpan, Toulouse, France.
authors.forename: Marie-Paule
authors.initials: MP
authors.lastname: Roth
authors.affiliation: Department of Pathology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
authors.forename: Heikki
authors.initials: H
authors.lastname: Helin
authors.affiliation: Department of Bacteriology and Immunology and Department of Physiology, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
authors.forename: Olli
authors.initials: O
authors.lastname: Ritvos
mesh_terms: D028341:Activins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D064591:Allografts / Q000276:immunology*; D000818:Animals; D016207:Cytokines / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate; D007249:Inflammation; D007668:Kidney / Q000276:immunology*; D016030:Kidney Transplantation; D008297:Male; D010865:Pilot Projects; D051381:Rats; D017208:Rats, Wistar; D051437:Renal Insufficiency / Q000601:surgery; D015427:Reperfusion Injury; D015398:Signal Transduction; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014184:Transplantation, Homologous
chemical_list: D016207:Cytokines; D016212:Transforming Growth Factor beta; C422405:activin A; C044147:activin B; D028341:Activins
keywords: activin; innate immunity; ischemia-reperfusion injury; kidney transplantation; transforming growth factor-beta