Interleukin-1β Increases the Biosynthesis of the Heat Shock Protein hsp70 and Selectively Decreases the Biosynthesis of five Proteins in rat Pancreatic Islets

Abstract

Prolonged exposure to high concentrations of human recombinant interleukin-1β (rIL-1β) has been reported to exert both suppressive and cytotoxic effects on pancreatic β-cells during culture in vitro. In order to investigate the molecular mechanism(s) underlying the actions of rIL-1β on the β-cell, we have exposed isolated rat pancreatic islets for 3 or for 24 h to 25U/ml of rIL-1β. Subsequently the biosynthesis of heat shock proteins, as assessed by western blot analysis, and total protein biosynthesis patterns were studied, using one and two-dimensional gel electrophoresis of [³⁵S]methionine labelled islet proteins from different subcellular compartments.

It was found that rIL-1β exerted no specific effects on protein synthesis when added during a 3h incubation period. However, after a 24 h incubation period, the synthesis of a group of acidic proteins with the approximate molecular weight of 35 kD was specifically inhibited in the rIL-1β treated islets. This alteration was predominantly associated with the endoplasmic reticulum fraction. The cytokine also inhibited the synthesis of four cytosolic proteins with the molecular weights 75, 85, 95 and 120 kD. In contrast. rIL-1β increased the expression of the heat shock protein hsp70 both in the microsomal and cytosolic fractions, in contrast to the islet nuclei in which no increase was found.

These results show that exposure of pancreatic islets to rIL-1β is accompanied by specific alterations in the protein synthesis of the islet cells. The formation of the hsp70 may reflect either a defense mechanism by the β-cell or a direct effect of the cytokine.

Key Words:

• Heat shock protein
• interleukin-I
• pancreatic islets
• protein synthesis