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Mediators of Inflammation
Volume 8, Issue 2, Pages 85-91
http://dx.doi.org/10.1080/09629359990577

The Destructive Action of IL-1α and IL-1β in IDDM is a Multistage Process: Evidence and Confirmation by Apoptotic Studies, Induction of Intermediates and Electron Microscopy

1Department of Biology, University of Crete, P.O. Box 2208, Crete, Heraklion 714-09, Greece
2Department of Pathology, Immunology laboratory, Medical School, University of Ioannina, Ioannina, Greece
3Laboratory of Biochemistry and Biophysics, Faculty of Agricultural Technology, Technical Educational Institute of Epirus, Arta, Greece

Copyright © 1999 Hindawi Publishing Corporation. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Using the rat β-cell RIN-5AH insulinoma line as a means for studying insulin-dependent diabetes mellitus (IDDM), it is shown that interleukin-1 (IL-1) induces β-cell damage initiated by early apoptotic signals. This action is demonstrated by DNA fragmentation, as assessed by specific BrdU labeling, surface expression of Fas and nitric oxide (NO) production. In addition, the interplay between NO and Fas is shown, while scanning electron microscopy (SEM) confirms apoptosis by revealing the degree and type of cellular damage which, in the case of IL-1α, can be reversed by an inhibitor to NO synthesis. Apoptosis is also reconfirmed by transmission electron microscopy (TEM) by observing condensed nuclear chromatin after IL-1 exposure. Thus, treatment of insulinoma cells with IL-1α and IL-1β seems to initiate a number of signals, including PKC activation as published previously, that ultimately lead to β-cell destruction. Each IL-1 isoform, however, definitely follows a different pathway of action.