Endocrine Abstracts

Lipocalin-2 (LCN-2) is known to act as an antiinflammatory or a proinflammatory mediator. Recently, LCN-2 has been recognized to play a role in obesity and insulin resistance. However, there is no knowledge about the expression and the role of LCN-2 in pancreatic islet β-cells. Therefore, we examined molecular mechanisms by which proinflammatory cytokines interleukin 1β (IL1β) and interferon γ (IFNγ) induce LCN-2 expression in RINm5F β-cells. IL1β significantly induced LCN-2 protein and mRNA expression. INFγ alone did not induce LCN-2 protein and mRNA expression whereas IFNγ significantly stimulated IL1β-induced LCN-2 expression. However, promoter study and EMSA showed that INFγ failed to stimulate IL1β-induced LCN-2 promoter activity and binding activity of NFκB on LCN-2 promoter. Meanwhile, western blot using NFκB inhibitor and promoter assay using truncated constructs showed that NFκB was a key factor in IL1β-induced LCN-2 expression. However, NFκB and STAT-1 were not involved in stimulatory effect of INFγ on IL1β-induced LCN-2 expression. Furthermore, we found that LCN-2 expression was significantly increased and prolonged compared with both iNOS and COX-2 expression under exposure to IL1β, and that LCN-2 receptor was expressed in pancreatic β-cells. Our data suggest that IL1β induced LCN-2 expression via NFκB activation and IFNγ significantly stimulated IL1β-induced LCN-2 expression at protein and mRNA level but not at promoter activity. This effect of INFγ was not independent of NFκB and STAT-1 activation. In addition, abundant expression of LCN-2 and LCN-2 receptor in β-cells implies that LCN-2 plays a role in β-cell function. Our data suggest that IFN-γ significantly potentiates IL1β-induced LCN-2 expression at mRNA and protein level but not at promoter level, and NFκB plays a key role in IL1β-induced LCN-2 expression. In addition, abundant expression of LCN-2 and LCN-2 receptor in β-cells implies that LCN-2 plays a role in β-cell function.