Endocrine Abstracts (2004) 7 P23

Effects of estrogen on leptin signalling and leptin-induced TNF-alpha production

M Fazeli1, SH Zarkesh-Esfahani1,2, M Maamra1 & RJM Ross1

1Division of Clinical Sciences (North), University of Sheffield, Sheffield, UK; 2Department of Biology, The University of Isfahan, Isfahan, Iran.

Introduction: Leptin modulates immune activation in relation to nutritional state and there is gender difference in body composition and the immune response. Leptin induces the release of pro-inflammatory cytokines, including TNF-alpha, from human peripheral blood mononuclear cells (PBMCs). We hypothesised that estrogen may modulate the immune actions of leptin. Aim: To test the effect of estrogen on leptin signalling and leptin-induced TNF-alpha production. Materials and Methods: The impact of estrogen on leptin signalling was measured using a STAT3 responsive reporter plasmid (SIE-TK-luc) bioassay in the estrogen receptor positive MCF-7 cell line. To test the impact of estrogen on leptin-induced TNF-alpha production by PBMCs, FACS and ELISA analysis were performed. For FACS analysis, TNF-alpha immunostaining was measured 6 hours after treatment of whole blood with leptin and estrogen. In the ELISA analysis TNF-alpha was measured in cell conditioned medium of isolated PBMCs after 2 days incubation with estrogen and leptin. Results: Leptin induced a dose dependent increase in SIE activation, whereas estrogen alone had no effect. Estrogen addition in leptin-treated cells inhibited leptin-induced SIE activation (Fold induction 8.1 plus/minus 0.2 leptin vs 3.85 plus/minus 0.2 leptin plus estrogen). In human monocytes, FACS studies showed that estrogen alone had no effect on TNF-alpha production. In contrast, leptin induced TNF-alpha production. Co-treatment of leptin and estrogen inhibited the effect of leptin on TNF-alpha production (Fold induction 7.4 plus/minus 1.0 leptin vs 4.8 plus/minus 0.6 leptin plus estrogen). Similarly, the ELISA showed that leptin induces TNF-alpha release from PBMCs and co-treatment with estrogen inhibited leptin's action (Fold induction 2.6 plus/minus 0.2 leptin vs 1.9 plus/minus 0.2 leptin plus estrogen). Conclusion: Estrogen can inhibit the signalling and immune actions of leptin. This could be one factor explaining the sexual dimorphism observed in the immune response.

Article tools

My recent searches

No recent searches.