Heme Oxygenase-1 Induction in Islet Cells Results in Protection from Apoptosis and Improved in Vivo Function after Transplantation

Antonello Pileggi, R. Damaris Molano, Thierry Berney, Pierre Cattan, Caterina Vizzardelli, Robert Oliver, Christopher Fraker, Camillo Ricordi, Ricardo L. Pastori, Fritz H. Bach, Luca Inverardi

Research output: Contribution to journalArticle

213 Scopus citations

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 β-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.

Original languageEnglish (US)
Pages (from-to)1983-1991
Number of pages9
JournalDiabetes
Volume50
Issue number9
DOIs
StatePublished - Sep 2001

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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