(A) Activation of STAT3 by leptin. Cell lysates from the indicated cell lines, either untreated (–) or treated for 45 min with 100 ng/ml leptin (Lep), were analyzed for STAT3 activation by Western blot with anti-phospho-STAT3, along with anti-STAT3 and anti-GAPDH to confirm equivalent loading. Experiments were performed thrice and blots are representative from one experiment (Supplementary Figure 4). (B) Induction of STAT3 DNA binding activity by leptin. Nuclear extracts from the indicated cell lines, either untreated (–) or treated for 45 min with 100 ng/ml leptin (Lep), interleukin-6 (IL-6), or leptin and leptin-inhibitor (inh) and analyzed for STAT3 activation by EMSA with a STAT3 (m63) probe. Experiments were performed thrice and blots are representative of one experiment. (C-D) Expression of STAT3 responsive genes by leptin. Cells, either untreated (–) or treated with 100 ng/ml leptin (Lep), were analyzed by semi-quantitative RT-PCR (C), with the fold change and SEM quantified by subsequent Real-Time RT-PCR (D) (*p<0.05). (E-F) Induction of STAT3 target gene products by leptin. PA1 cells, either untreated (–) or treated with 100 ng/ml leptin (Lep), were analyzed by gelatin zymography for MMP9 (E) and Western blot analysis for ICAM-1, BCL2 and GAPDH (F). (G) Leptin-induced STAT3 activation is blocked by specific inhibitors of the JAK2/STAT3 pathway. Lysates were prepared from cells, either untreated (–) or treated with 100 ng/ml leptin (Lep), without inhibitors (con) or with specific inhibitors for STAT3 (S3I) or JAK2 (J2I), as indicated, and analyzed for STAT3 phosphorylation as per panel A (Supplementary Figure 5).