The Effect of Transforming Growth Factor β1,and Tumor Necrosis Factor α on the Cytotoxic-Cytostatic Action of Interleukin-1 (α and β Isoforms) on the Pancreatic B Cell Line Rin-5ah

Abstract

The rat pancreatic β cell line RIN-5AH was treated with the cytokines IL-1 (α and β), TNFα and TGF-β1, in order to examine at the clonal level the reported mostly cytotoxic effects of IL-1, on isolated islets of Langerhans and islet cell preparations. In contrast to what has been previously reported for whole islets and islet cell preparations we find that IL-1 (α or β) is not cytotoxic to the RIN-5AH cells in logarithmic growth phase to any extent, even at very high cytokine concentrations (125 nM). Furthermore, TNFα does not in any way potentiate IL-1 cytotoxicity. Transforming growth factor-β1 (TGF-β1) at concentrations of 80 pM to 2 nM, has a potentiating effect on IL-1 cytotoxicity (conc. 5 nM) for this clonal cell line. The effect is proportional to the level of TGF-β1 present and is exerted regardless of the IL-1 isoform used. The effects of the various cytokines, alone or in combination, were only observed at high (25 mM) glucose concentrations, and no such effects were observed at the physiological (5 mM) glucose concentration. Furthermore the combination of TGF-β1 and IL-1 inhibits the release of insulin by these cells, whereas either cytokine alone has no effect.

We conclude that the RIN-5AH cells in showing little cytotoxic/cytostatic response to IL-1 are responding more as isolated β cells than as cells within islets. The potentiation of the action of IL-1 by TGF-β1 on these cells is a matter of further investigation.