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Mediators of Inflammation
Volume 4, Issue 5, Pages 374-379

IL-6-mediated MHC class II induction on RIN-5AH insulinoma cells by IFN-γ occurs via the G-protein pathway

1Department of Biology, University of Crete, P.O. Box 1470, Crete, Heraklion GR-71110, Greece
2Laboratory of Immunology, Department of Internal Medicine, University of Ioannina Medical School, Ioannina GR-451 10, Greece

Copyright © 1995 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.


Major histocompatibility complex (MHC) class II antigen expression has been implicated in the pathogenesis of autoimmune type 1 diabetes. In this study we examined the role of various cytoldnes that may induce MHC class II surface antigen expression, using the rat insulinoma line RIN-5AH as a pertinent model system. As in another study, the ability of IFN-γ to amplify MHC class II antigen expression 4-fold is demonstrated. At the same time we noted a 5-fold increase of these histocompatibility antigens by IL-6. Signal transduction analysis reveals that IL-6-induced MHC class II expression is specifically mediated by the G-protein system (activation of p21ras by IL-6) since mevalonic acid lactone (a Gprotein inhibitor) abolishes the action of IL-6. In contrast, IFN-γ, which does not activate p21ras, is not inhibited by protein kinase C (PKC) inhibitors but by those of the G-protein pathway. This finding raises the possibility that IFN-γ induces RIN cells to secrete IL-6 (as shown previously, as well as in this paper) which, in turn, increases class II antigen expression via the G-protein pathway. This action may be unique to IL-6 or in synergy with IFN-γ. Other cytokines such as IL-1α and β, and TNF-α induce a smaller increase in MHC class II antigens on RIN cells, and appear to activate both the G-protein and the PKC signal transduction pathways to varying degrees. Therefore, injury of pancreatic β-cells and possible induction of autoimmune type 1 diabetes via various cytokines may be caused by IL-6 or IFN-γ, or by their ability to induce MHC class II antigen upregulation.