Leptin exerts an anti-apoptotic effect on human dendritic cells via the PI3K-Akt signaling pathway.
Leptin is an adipocyte-derived hormone/cytokine that modulates immune responses. It induces functional and morphological changes in human dendritic cells (DCs), licensing them towards Th1 priming and promoting DC survival. Here we found that leptin protects DCs from spontaneous, UVB and H(2)O(2)-induced apoptosis, by triggering the activation of nuclear factor-kappa B (NF-kappaB) and a parallel up-regulation of bcl-2 and bcl-XL gene expression and Akt activation. We found that leptin activates the PI3K-Akt signaling pathway as demonstrated by the suppression of the effect of leptin on DC survival by wortmannin and API-2, which suppress the leptin-induced activation of Akt, NF-kappaB, bcl-2, bcl-XL and protection from apoptosis. These results provide insights on the immunoregulatory function of leptin, supporting a potential application in immunotherapeutic approaches.
Mattioli
Benedetta
B
Department of Therapeutic Research and Medicine Evaluation, Istituto Superiore di Sanità, Rome, Italy.
Giordani
Luciana
L
Quaranta
Maria Giovanna
MG
Viora
Marina
M
D000730:Androstadienes / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology* / Q000528:radiation effects; D002470:Cell Survival / Q000187:drug effects / Q000276:immunology / Q000528:radiation effects; D002478:Cells, Cultured; D002747:Chlorpropamide / Q000031:analogs & derivatives / Q000494:pharmacology; D003713:Dendritic Cells / Q000166:cytology / Q000201:enzymology / Q000276:immunology*; D004789:Enzyme Activation / Q000187:drug effects / Q000276:immunology / Q000528:radiation effects; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology / Q000528:radiation effects; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D020738:Leptin / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D016328:NF-kappa B / Q000276:immunology / Q000378:metabolism; D016877:Oxidants / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000276:immunology* / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology* / Q000528:radiation effects; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D014466:Ultraviolet Rays; D000077191:Wortmannin; D051020:bcl-X Protein / Q000276:immunology / Q000378:metabolism; D000096926:Benzenesulfonamides
D000730:Androstadienes; D002747:Chlorpropamide; D006861:Hydrogen Peroxide; D020738:Leptin; D016328:NF-kappa B; D016877:Oxidants; D019869:Phosphatidylinositol 3-Kinases; D047428:Protein Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D000077191:Wortmannin; D051020:bcl-X Protein; C111224:API 2; D000096926:Benzenesulfonamides; C494811:BCL2L1 protein, human