Interleukin-1 beta induces the expression of hsp70, heme oxygenase and Mn-SOD in FACS-purified rat islet beta-cells, but not in alpha-cells

The cytokine IL-1 beta has previously been demonstrated to induce the expression of the stress genes iNOS, hsp70, heme oxygenase and Mn-SOD in rat pancreatic islets in vitro. The aim of this study was to determine whether the IL-1 beta-induced effects are specific for the insulin producing beta-cell, or whether other islet cells, such as the glucagon-producing alpha-cell, respond to IL-1 beta addition. Purified rat alpha- and beta-cell suspensions were obtained by fluorescence-activated cell sorting and incubated with or without IL-1 beta (25 U/ml) for 24 h. The alpha- and beta-cell contents of hsp70, heme oxygenase and Mn-SOD and medium nitrite levels were determined. It was found that IL-1 beta exposure induced the production of nitric oxide in beta-cells, but not in alpha-cells. Moreover, the expression of hsp70, heme oxygenase and Mn-SOD was also induced in beta-cells, but not in alpha-cells. There were no detectable levels of hsp70 in alpha-cells. It is concluded that the stress gene response following IL-1 beta exposure is markedly different in alpha- and beta-cells. This finding may be of importance for the understanding of the autoimmune destruction of beta-cells in insulin-dependent diabetes mellitus.