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. 2010 Dec 7;104(1):128–137. doi: 10.1038/sj.bjc.6606013

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Copyright © 2011 Cancer Research UK

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Signalling mechanisms for leptin regulation of IL-1 system in 4T1 cells. Leptin upregulated IL-1 system at transcriptional and translational levels. Leptin canonical signalling pathways (JAK2/STAT3, MAPK and PI-3K/AKT1) were mainly involved in the upregulation of IL-1 system. Leptin activation of PI-3K/AKT1 was related to the phosphorylation of mTOR and its downstream target, 4E-BP1, which is probably linked to upregulation of IL-1β and IL-1Ra. In addition, mTOR negatively regulated IL-1α. Leptin upregulation of IL-1α promoter involved the activation of SP1 and NF-κB. Leptin-induced non-canonical signalling pathways (PKC, p38 and JNK) differentially impacted on the expression of some components of IL-1 system. Leptin-induced upregulation of VEGF/VEGFR2 system was partially mediated by IL-1/IL-1R tI signalling.