Induction mechanism of lipocalin-2 expression by co-stimulation with interleukin-1β and interferon-γ in RINm5F beta-cells

Lipocalin-2 (LCN-2) was known to play a role in obesity and insulin resistance, however, little is known about the expression of LCN-2 in pancreatic islet beta-cells. We examined the molecular mechanisms by which proinflammatory cytokines interleukin-1 beta (IL-1 beta) and interferon-gamma (IFN-gamma) induce LCN-2 expression in RINm5F beta-cells. IL-1 beta significantly induced LCN-2 expression while IFN-gamma alone did not induce it. IFN-gamma significantly potentiated IL-1 beta-induced LCN-2 protein and mRNA expression. However, promoter study and EMSA showed that IFN-gamma failed to potentiate IL-1 beta-induced LCN-2 promoter activity and binding activity of transcription factors on LCN-2 promoter. Furthermore, LCN-2 mRNA stability and transcription factors NF-kappa B and STAT-1 were not involved in the stimulatory effect of IFN-gamma on IL-1 beta-induced LCN-2 expression. Meanwhile, Western Blot and promoter analyses showed that NF-kappa B was a key factor in IL-1 beta-induced LCN-2 expression. Collectively, IL-1 beta induces LCN-2 expression via NF-kappa B activation in RINm5F beta-cells. IFN-gamma potentiates IL-1 beta-induced LCN-2 expression at mRNA and protein levels, but not at promoter level and the stimulatory effect of IFN-gamma is independent of NF-kappa B and STAT-1 activation. These data suggest that LCN-2 may play a role in beta-cell function under an inflammatory condition. (C) 2013 Elsevier Inc. All rights reserved.