Leptin receptor (Ob-R) expression is induced in peripheral blood mononuclear cells by in vitro activation and in vivo in HIV-infected patients.
Leptin, the Ob gene product, is an adipocyte hormone that centrally regulates weight control. In addition, other effects of leptin in peripheral tissues have been described. Thus, leptin has been found to regulate reproduction, haematopoiesis and immune function. We have found recently that leptin has a stimulatory effect on human peripheral blood mononuclear cells (PBMC). Monocytes are activated by leptin alone whereas T lymphocytes need a suboptimal stimulus of PHA or ConA before further activation by leptin. These effects are mediated by the long isoform of the leptin receptor, which has been shown to trigger signalling in PBMC. In fact, we have found that human leptin stimulates Janus kinase (JAK)-signal transducer and activator of transcription (STAT), phosphatidylinositol 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) pathways in PBMC. In order to assess possible regulation of the long isoform of the leptin receptor (Ob-R) in mononuclear cells upon activation, we have studied the expression of Ob-R by RT-PCR and Western blotting in PBMC activated in vitro by PHA or ConA and in vivo in HIV-infected patients. We have found that in vitro activation and in vivo HIV infection correlates with an increase in leptin receptor expression in PBMC. Moreover, the leptin receptor is tyrosine phosphorylated in PBMC from HIV-infected patients, suggesting that the leptin receptor is activated. These results are consistent with the suggested role of leptin in modulating the immune response.
Sánchez-Margalet
V
V
Department of Clinical Biochemistry, Internal Medicine, Virgen Macarena University Hospital, Seville, Spain. margalet@us.es
Martín-Romero
C
C
González-Yanes
C
C
Goberna
R
R
Rodríguez-Baño
J
J
Muniain
M A
MA
D000293:Adolescent; D000328:Adult; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D002478:Cells, Cultured / Q000378:metabolism; D002648:Child; D003208:Concanavalin A / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D015658:HIV Infections / Q000150:complications / Q000276:immunology*; D006526:Hepatitis C / Q000150:complications / Q000276:immunology; D006801:Humans; D020738:Leptin / Q000494:pharmacology / Q000502:physiology*; D008213:Lymphocyte Activation / Q000187:drug effects / Q000235:genetics*; D008297:Male; D010766:Phosphorylation; D010835:Phytohemagglutinins / Q000494:pharmacology; D020033:Protein Isoforms / Q000096:biosynthesis* / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D011499:Protein Processing, Post-Translational; D012333:RNA, Messenger / Q000096:biosynthesis; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism*
D002352:Carrier Proteins; C515448:LEPR protein, human; D020738:Leptin; D010835:Phytohemagglutinins; D020033:Protein Isoforms; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; D011994:Recombinant Proteins; D003208:Concanavalin A