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

• Published in: Biochemical and biophysical research communications 2013-05, Vol.434 (3), p.577-583
• Main Authors: Chang, Seo-Yoon, Kim, Dong-Bin, Ko, Seung-Hyun, Jo, Yang-Hyeok, Kim, Myung-Jun
• Format: Article
• Language: English
• Subjects: Animals; Base Sequence; Binding Sites; Cell Line; DNA Primers; Electrophoretic Mobility Shift Assay; Interferon-gamma - pharmacology; Interferon-γ; Interleukin-1beta - pharmacology; Interleukin-1β; Islets of Langerhans - drug effects; Islets of Langerhans - metabolism; Lipocalin-2; Lipocalins - genetics; Lipocalins - metabolism; Molecular Sequence Data; NF-kappa B - metabolism; NF-κB; Rats; Real-Time Polymerase Chain Reaction; RINm5F cells; RNA, Messenger - genetics; RNA, Messenger - metabolism
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2013.03.117

•Little is known about the expression mechanism of LCN-2 in islet β-cells.•We examined expression mechanism of LCN-2 by IL-1β and IFN-γ in RINm5F β-cells.•IL-1β induces LCN-2 expression via NF-κB activation.•IFN-γ increases LCN-2 induction by IL-1β at mRNA and protein but not promoter level.•The stimulatory effect of IFN-γ is independent of NF-κB and STAT-1 activation. 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.