Induction mechanism of lipocalin-2 expression by co-stimulation with interleukin-1¦Â and interferon-¦Ã in RINm5F beta-cells

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• 作者：Seo-Yoon Chang^a ; ¹ ; Dong-Bin Kim^b ; ¹ ; Seung-Hyun Ko^b ; Yang-Hyeok Jo^a ; Myung-Jun Kim^a ; ^{mjunkim@catholic.ac.kr}
• 关键词：IL-1¦Â ; interleukin-1¦Â ; IFN-¦Ã ; interferon-¦Ã ; LCN-2 ; lipocalin-2 ; NF-¦ÊB ; nuclear factor-¦ÊB ; iNOS ; inducible nitric oxide synthase ; EMSA ; electrophoretic mobility shift assay
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2013
• 出版时间：10 May, 2013
• 年：2013
• 卷：434
• 期：3
• 页码：577-583
• 全文大小：1412 K

文摘

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