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

Abstract

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 β-cells. We examined the molecular mechanisms by which proinflammatory cytokines interleukin-1β (IL-1β) and interferon-γ (IFN-γ) induce LCN-2 expression in RINm5F β-cells. IL-1β significantly induced LCN-2 expression while IFN-γ alone did not induce it. IFN-γ significantly potentiated IL-1β-induced LCN-2 protein and mRNA expression. However, promoter study and EMSA showed that IFN-γ failed to potentiate IL-1β-induced LCN-2 promoter activity and binding activity of transcription factors on LCN-2 promoter. Furthermore, LCN-2 mRNA stability and transcription factors NF-κB and STAT-1 were not involved in the stimulatory effect of IFN-γ on IL-1β-induced LCN-2 expression. Meanwhile, Western Blot and promoter analyses showed that NF-κB was a key factor in IL-1β-induced LCN-2 expression. Collectively, IL-1β induces LCN-2 expression via NF-κB activation in RINm5F β-cells. IFN-γ potentiates IL-1β-induced LCN-2 expression at mRNA and protein levels, but not at promoter level and the stimulatory effect of IFN-γ is independent of NF-κB and STAT-1 activation. These data suggest that LCN-2 may play a role in β-cell function under an inflammatory condition.