
-   LCN2 protects against infection and sepsis and shapes intestinal microbial community structures by binding enterobactin type siderophores, thereby preventing bacterial iron acquisition and the growth of siderophore-dependent strains [PMID: 28214071].
-   The role of LCN-2 in protecting again infection was demonstrated in LCN-2 deficient mice - when challenged with sub lethal dose of E.Coli, mice demonstrated markedly increased bacteraemia and bacterial burden compared to normal controls. The bacteriostatic effect of LCN-2 was absolutely specific for bacteria that acquire iron through LCN-2-binding siderophores (for example enterochelin and mycobactin) [PMID: 15531878].
-   In mouse CKD model Lcn2 expression was elevated following EGFR activation and mediated EGFR's mitogenic effects during renal deterioration. Hif-1alpha was essential for EGFR-induced Lcn2 overexpression [PMID: 20921623].
-   In psoriasis model Lcn2 stimulated human neutrophils to produce proinflammatory mediators via 24p3R and activated the ERK1/2 and p38 MAPK signaling pathways, which also mediated Lcn2-induced neutrophil chemotaxis in vitro [PMID: 26979478].

## Summary

The LCN2 gene encodes Lipocalin-2, a protein involved in iron trafficking, innate immunity, and apoptosis regulation [CS: 10]. This protein binds iron through association with the siderophore 2,3-dihydroxybenzoic acid and mediates iron transport into and out of cells, which is essential in both iron regulation and limiting bacterial growth [CS: 9].

Liver diseases often involve inflammation and infection, where LCN2 expression increases as part of the innate immune response [CS: 9]. In conditions like partial hepatectomy or hepatitis infections, there is elevated expression of LCN2 mRNA in the liver together with higher concentrations in plasma [CS: 8]. The upregulation of LCN2 in these scenarios is attributable to the need for iron sequestration to inhibit bacterial proliferation: LCN2 binds to iron-laden siderophores, like bacterial enterobactin, effectively starving pathogens of the iron essential for their growth [CS: 9]. Additionally, in ob/ob mice with ethanol-induced liver injury or in various liver tumors, elevated hepatic LCN2 expression suggests a response to tissue damage and stress, where its iron-binding and transport properties potentially modulate the local iron homeostasis and influence tissue repair processes [CS: 7]. Increased LCN2 transcription is a direct result of proinflammatory cytokines like TNFalpha, IFNgamma, and IL-6, which are activated in inflammatory conditions [CS: 9], while interactions with pathogens stimulate immune receptors like TLR4, enhancing LCN2 production to bolster the local immune defense by controlling iron availability and limiting microbial growth [CS: 8].
