Differential effects of interleukin-13 and interleukin-6 on Jak/STAT signaling and cell viability in pancreatic β-cells
Russell, Mark A.
Cooper, Angela C.
Morgan, Noel G.
Taylor & Francis
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Pro-inflammatory cytokines are important mediators of β-cell demise in type 1 diabetes, and similar mechanisms are increasingly implicated in type 2 diabetes, where a state of chronic inflammation may persist. It is likely that the actions of anti-inflammatory cytokines are also altered in diabetes. Cytokines are released from immune cells, which may be recruited to the islets in diabetes, but they can also be produced by islet endocrine cells in response to environmental factors, including enteroviral infection. Since enteroviral infection of islet cells may influence the development of diabetes in humans, we examined the actions of two cytokines, IL-13 and IL-6, whose expression are reported to be altered in β-cells during enteroviral infection. Human and rodent islet cells were shown to express receptors for both IL-13 and IL-6, and treatment with either cytokine resulted in the rapid phosphorylation of STAT3 and STAT6. However, while β-cells were protected against a range of cytotoxic insults during exposure to IL-13, treatment with IL-6 enhanced cytotoxicity and western blotting revealed that IL-13 induced one specific isoform of phospho-STAT6 preferentially. Upon incubation with both cytokines together, the isoform of STAT6 that was upregulated by IL-13 alone was again induced, and the effects of IL-6 on β-cell viability were attenuated. Overall, the results suggest that induction of specific isoforms of STAT family transcription factors may underlie the cytoprotective actions of IL-13, and they imply that selective targeting of specific STAT-mediated signaling components could provide a means to ameliorate the loss of β-cell viability in diabetes.
Nuffield Foundation - Bursary scheme
European Union’s Seventh Framework Programme PEVNET (FP7/2007-2013)
This is an Accepted Manuscript of an article published by Taylor & Francis in islets on 1 March 2013, available online: http://www.tandfonline.com/10.4161/isl.24249
Open Access article
Vol. 5 (2), pp. 95 - 105
Place of publication
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