IL-1 beta transduces different signals than IL-1 alpha leading to class II antigen expression on beta-insulinoma RIN-5AH cells through specific receptors

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peer-reviewed

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J Recept Signal Transduct Res

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Like most cytokines, IL-1 transduces its signals for growth, differentiation and diverse cellular functions after binding to specific receptors on the cell surface. Up to now two IL-1 receptors have been reported, type I which induces signal transduction and type II which binds IL-1 but does not transduce signalling. By using the rat insulinoma RIN-5AH cell line that expresses both types of receptor mRNA, and computer-assisted binding analysis, we show that interleukin-1 beta (IL-1 beta) binds to a single class of high affinity receptors with a Kd of 155 pmol/l. The average number of receptors on adherent cell layer is calculated to be 7300 per cell. 125I-IL-1 beta binding can be competed out by unlabelled IL-1 beta. 125I-IL-1 alpha binding can be also obtained and is subject to competition by cold IL-1 alpha. Its saturation curve, however, varies within experiments due to differential receptor up-regulation. These results have also been confirmed by FACS analysis using specific antibodies to type I and II IL-1 receptors, where type I receptor antibody binds strongly to RIN-5AH cells, and type II receptor antibody shows weak staining, also due to inadequate receptor up-regulation. In order to determine whether functional signal transduction occurs via the receptors detected, it is shown that IL-1 beta is able to induce MHC class II antigen expression on the surface of the RIN cells, whereas IL-1 alpha is unable to do so, indicating different signal reception by the cells. IL-1 beta-induced class II upregulation shows moderate signs of p21ras or/and PKC dependency, whereas IL-1 alpha strongly activates both pathways that probably regulate different functions. Finally, both IL-1 alpha and beta induce nitric oxide (NO) production in a time-dependent fashion which appears to be unrelated to the signals and pathways described, but may be involved in the onset of autoimmune type 1 diabetes.

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Λέξεις-κλειδιά

Animals, Dose-Response Relationship, Drug, Flow Cytometry, Histocompatibility Antigens Class II/*metabolism, Insulinoma/*metabolism, Interleukin-1/*metabolism, Kinetics, Nitric Oxide/biosynthesis, Pancreatic Neoplasms/*metabolism, Rats, Receptors, Interleukin-1/metabolism, *Signal Transduction, Tumor Cells, Cultured

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http://www.ncbi.nlm.nih.gov/pubmed/9029492
http://informahealthcare.com/doi/abs/10.3109/10799899709036605

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en

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Γενική Περιγραφή / Σχόλια

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Πανεπιστήμιο Ιωαννίνων. Σχολή Επιστημών Υγείας. Τμήμα Ιατρικής

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