Authors: Kaminski, A.; Kaminski, E. R.; Morgan, N. G.

Source: Clinical & Experimental Immunology, Volume 148, Number 3, June 2007 , pp. 583-588(6)

Publisher: Wiley-Blackwell

Abstract:

Summary

Loss of pancreatic β-cells in type I diabetes is associated with an increase in T helper 1 (Th1) proinflammatory cytokines in the islet milieu, with a concomitant reduction in Th2 anti-inflammatory cytokines. In animal models, manoeuvres designed to polarize Th1 responses towards Th2, particularly involving interleukin (IL)-4, have been shown to protect against insulitis and diabetes. The aim of this study was to determine whether IL-4 can exert a direct effect on β-cell viability. The rat pancreatic β-cell line, BRIN-BD11, was used. IL-4R mRNA expression was assayed by reverse transcription-polymerase chain reaction and DNA sequencing and protein expression measured using anti-IL-4R antibodies and confocal microscopy. Cells were pretreated in vitro with IL-4, incubated with IL-1β and interferon (IFN)-γ and DNA fragmentation and nitrite production analysed by flow cytometry and Griess assay, respectively. Expression of type I (IL-4R alpha and common γ-chain) and type II (IL-4R alpha, IL-13R alpha-1) IL-4R mRNA transcripts, together with cell surface expression of IL-4R, was demonstrated. Pre-incubation with IL-4 reduced significantly cell death induced by IL-1β alone or by a combination of IL-1β and IFN-γ, although this was not accompanied by a reduced production of nitrite. The protective effect of IL-4 was not seen when all three cytokines were added simultaneously. These results demonstrate, for the first time, expression of IL-4 receptor components on rat pancreatic β-cells and reveal a direct protective effect on the loss of viability mediated by proinflammatory cytokines when β-cells are pre-incubated with IL-4.

Keywords: apoptosis; interferon-γ; interleukin-1β; interleukin-4; islet cells; pancreatic β cells

Document Type: Research article

DOI: http://dx.doi.org/10.1111/j.1365-2249.2007.03375.x

Publication date: 2007-06-01

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