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Human leptin promotes survival of human circulating blood monocytes prone to apoptosis by activation of p42/44 MAPK pathway.
- Source :
-
Cellular immunology [Cell Immunol] 2002 Dec; Vol. 220 (2), pp. 143-9. - Publication Year :
- 2002
-
Abstract
- Leptin, the adipocyte-secreted hormone, is known to function as an immunomodulatory regulator. Thus, we have recently found that human leptin promotes stimulation and proliferation of human peripheral blood mononuclear cells. Besides, we have also demonstrated that leptin triggers PI3K and p42/44 MAPK signaling pathways. In the present work, we sought to study the possible effect of leptin on cell survival and apoptosis, as well as the mechanisms underlying these effects. We have cultured human PBMC in serum-free conditions to assess the effect of leptin on cell survival and apoptosis. We have assayed the early phases of apoptosis by flow cytometric detection of phosphatidylserine expression using fluorescein isothiocyanate (FITC)-labelled Annexin V, simultaneously with dye exclusion of propidium iodide (PI), to discriminate intact cells, apoptotic, and necrotic cells. We have found that leptin promotes dose-dependent cell survival of monocytes after 24-96 h of serum-free culture. This effect of leptin on monocyte survival was completely reversed by blocking p42/44 MAPK activation employing the MEK inhibitor PD98059, whereas it was not affected by PI3K inhibition using Wortmannin. Leptin promotes this survival effect by preventing the apoptosis of monocyte cells, via MAPK activation. Thus, p42/44 MAPK inhibition, using PD98059, but not PI3K inhibition, employing Wortmannin, blocked the protective effect of leptin preventing apoptosis of monocytes cultured in the absence of serum. These data suggest that leptin is a trophic factor for the survival of blood monocytes and this effect is mediated by the p42/44 MAPK pathway.
- Subjects :
- Androstadienes pharmacology
Annexin A5 chemistry
Cell Survival immunology
Dose-Response Relationship, Immunologic
Enzyme Activation
Enzyme Inhibitors pharmacology
Flavonoids pharmacology
Flow Cytometry
Fluorescent Dyes chemistry
Humans
Leptin blood
Leptin pharmacology
MAP Kinase Signaling System drug effects
Mitogen-Activated Protein Kinase 1 antagonists & inhibitors
Monocytes drug effects
Monocytes enzymology
Monocytes immunology
Phosphoinositide-3 Kinase Inhibitors
Propidium chemistry
Wortmannin
Apoptosis immunology
Leptin immunology
MAP Kinase Signaling System physiology
Mitogen-Activated Protein Kinase 1 metabolism
Monocytes cytology
Phosphatidylinositol 3-Kinases metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0008-8749
- Volume :
- 220
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Cellular immunology
- Publication Type :
- Academic Journal
- Accession number :
- 12657249
- Full Text :
- https://doi.org/10.1016/s0008-8749(03)00027-3