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

Autor: Heikki Helin, Johanna Savikko, Jukka Rintala, Ashok Kumar, Marie-Paule Roth, Arja Pasternack, Niina Palin, Olli Ritvos, Shivani Mistry, Bhanu Kalra
Jazyk: angličtina
Rok vydání: 2016
Předmět:
0301 basic medicine
Male
Time Factors
Pilot Projects
030230 surgery
Kidney
0302 clinical medicine
Transforming Growth Factor beta
Renal Insufficiency
Kidney transplantation
biology
Acute kidney injury
Allografts
3. Good health
Activins
surgical procedures
operative
Reperfusion Injury
embryonic structures
Cytokines
medicine.symptom
hormones
hormone substitutes
and hormone antagonists
Signal Transduction
medicine.medical_specialty
animal structures
Inflammation
Enzyme-Linked Immunosorbent Assay
03 medical and health sciences
Internal medicine
TGF beta signaling pathway
medicine
Animals
Humans
Transplantation
Homologous
Rats
Wistar
Transplantation
business.industry
Transforming growth factor beta
Dendritic cell
Fibroblasts
medicine.disease
Kidney Transplantation
Immunity
Innate
Rats
030104 developmental biology
Endocrinology
biology.protein
business
Follistatin
Zdroj: Transplant International. 30
ISSN: 0934-0874
DOI: 10.1111/tri.12876
Popis: 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.
Databáze: OpenAIRE
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