title: Expression of leptin receptors and response to leptin stimulation of human natural killer cell lines.
abstract: We previously reported that deficiency of leptin receptor (Ob-R(-/-), db/db) in mice led to impaired NK cell function. In the present paper, we, for the first time, found that human NK cell lines constitutively expressed leptin receptor (Ob-R), both long form Ob-R (Ob-R(L)) and short form Ob-R (Ob-R(S)), using immunohistochemical method, Western blotting, and RT-PCR assay. Interestingly, IL-2-dependent NK-92 cells proliferated without change in the presence or absence of leptin stimulation, but their cytotoxicity was dose-dependently responsible for leptin stimulation. The IL-2-independent YT cells were dose-dependently responsible for leptin stimulation to manifest rapid proliferation and strong cytotoxicity against tumor targets. In order to explain the mechanisms underlying the leptin function on NK cell lines, we examined the gene expression of cytokines (IL-2, IFNr), cytotoxic-associated molecules (perforin, FasL) and the activation of cytokine signal pathways (STAT1, STAT3). The results demonstrated that leptin activated the phosphorylation of STAT3 and then improved transcription of IL-2 and perforin genes. Our preliminary study indicates that leptin could affect NK cell function and may play an important role in innate immunity.
authors.affiliation: School of Life Sciences, University of Science and Technology of China, 443 Huangshan Road, Hefei City, Anhui 230027, China.
authors.forename: Yueran
authors.initials: Y
authors.lastname: Zhao
authors.forename: Rui
authors.initials: R
authors.lastname: Sun
authors.forename: Li
authors.initials: L
authors.lastname: You
authors.forename: Chunyi
authors.initials: C
authors.lastname: Gao
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Tian
mesh_terms: D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D003602:Cytotoxicity, Immunologic; D004268:DNA-Binding Proteins / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis / Q000235:genetics; D020014:K562 Cells; D007694:Killer Cells, Natural / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D020738:Leptin / Q000494:pharmacology*; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D054411:Receptors, Leptin; D050796:STAT3 Transcription Factor; D015534:Trans-Activators / Q000378:metabolism; D014158:Transcription, Genetic; D015854:Up-Regulation
chemical_list: D004268:DNA-Binding Proteins; D007376:Interleukin-2; C515448:LEPR protein, human; D020738:Leptin; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D015534:Trans-Activators; D054353:Perforin