title: 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.
authors.affiliation: Department of Physiology, College of Medicine, The Catholic University of Korea, Seoul, South Korea.
authors.forename: Seo-Yoon
authors.initials: SY
authors.lastname: Chang
authors.forename: Dong-Bin
authors.initials: DB
authors.lastname: Kim
authors.forename: Seung-Hyun
authors.initials: SH
authors.lastname: Ko
authors.forename: Yang-Hyeok
authors.initials: YH
authors.lastname: Jo
authors.forename: Myung-Jun
authors.initials: MJ
authors.lastname: Kim
mesh_terms: D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D017931:DNA Primers; D024202:Electrophoretic Mobility Shift Assay; D007371:Interferon-gamma / Q000494:pharmacology*; D053583:Interleukin-1beta / Q000494:pharmacology; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism; D000071068:Lipocalin-2; D054834:Lipocalins / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D017931:DNA Primers; D053583:Interleukin-1beta; C097278:Lcn2 protein, rat; D000071068:Lipocalin-2; D054834:Lipocalins; D016328:NF-kappa B; D012333:RNA, Messenger; D007371:Interferon-gamma