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- Title
Heme oxygenase-1 induction in islet cells results in protection from apoptosis and improved in vivo function after transplantation.
- Authors
Pileggi, Antonello; Molano, R. Damaris; Berney, Thierry; Cattan, Pierre; Vizzardelli, Caterina; Oliver, Robert; Fraker, Christopher; Ricordi, Camillo; Pastori, Ricardo L.; Bach, Fritz H.; Inverardi, Luca; Pileggi, A; Molano, R D; Berney, T; Cattan, P; Vizzardelli, C; Oliver, R; Fraker, C; Ricordi, C; Pastori, R L
- Abstract
Transplantation of islets of Langerhans represents a viable therapeutic approach for the treatment of type 1 diabetes. Unfortunately, transplanted islets are susceptible to allogeneic recognition and rejection, recurrence of autoimmunity, and destruction by local inflammation at the site of implantation. The last of these phenomena might not only result in functional impairment and death of islet cells but could also contribute to amplifying the subsequent specific immune response. Induction of islet cell protection against inflammation could therefore be postulated to be a powerful means to improve overall graft fate. Heme oxygenase-1 (HO-1) has been described as an inducible protein capable of cytoprotection via radical scavenging and apoptosis prevention. The purpose of the present study was to analyze whether HO-1 upregulation in a beta-cell line and in freshly isolated murine islets could result in protection from apoptosis and improve in vivo functional performance. HO-1 upregulation was induced reproducibly with protoporphyrins and was correlated with protection from apoptosis induced in vitro with proinflammatory cytokines or Fas engagement. Furthermore, in vivo HO-1 upregulation resulted in improved islet function in a model of marginal mass islet transplantation in rodents. Strategies aimed at inducing HO-1 upregulation might result in improved success in islet transplantation.
- Subjects
HEME oxygenase; ISLANDS of Langerhans; DIABETES; ALTERNATIVE medicine; ISLANDS of Langerhans transplantation; ANIMAL experimentation; APOPTOSIS; BIOCHEMISTRY; BLOOD sugar; COMPARATIVE studies; GENES; HOMOGRAFTS; PHENOMENOLOGY; RESEARCH methodology; MEDICAL cooperation; MEMBRANE proteins; MICE; OXIDOREDUCTASES; PORPHYRINS; REFERENCE values; RESEARCH; TIME; TUMOR necrosis factors; EVALUATION research; CANCER cell culture; PHYSIOLOGY
- Publication
Diabetes, 2001, Vol 50, Issue 9, p1983
- ISSN
0012-1797
- Publication type
journal article
- DOI
10.2337/diabetes.50.9.1983