Nitric oxide primes pancreatic β cells for Fas-mediated destruction in insulin-dependent diabetes mellitus

Giorgio Stassi, Ruggero De Maria, Giuliana Trucco, William Rudert, Roberto Testi, Aldo Galluzzo, Carla Giordano, Massimo Trucco

Research output: Contribution to journalArticlepeer-review

Abstract

Fas is an apoptosis-inducing surface receptor involved in controlling tissue homeostasis and function at multiple sites. Here we show that β cells from the pancreata of newly diagnosed insulin-dependent diabetes mellitus (IDDM) patients express Fas and show extensive apoptosis among those cells located in proximity to Fas ligand-expressing T lymphocytes infiltrating the IDDM islets. Normal human pancreatic β cells that do not constitutively express Fas, become strongly Fas positive after interleuken (IL)-β exposure, and are then susceptible to Fas-mediated apoptosis. N(G)-monomethyl-L- arginine, an inhibitor of nitric oxide (NO) synthase, prevents IL-β-induced Fas expression, whereas the NO donors sodium nitroprusside and nitric oxide releasing compound (NOC)-18, induce functional Fas expression in normal pancreatic β cells. These findings suggest that NO-mediated upregulation of Fas contributes to pancreatic β cell damage in IDDM.

Original languageEnglish
Pages (from-to)1193-1200
Number of pages8
JournalJournal of Experimental Medicine
Volume186
Issue number8
DOIs
Publication statusPublished - Oct 20 1997

ASJC Scopus subject areas

  • Immunology

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