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PMID:12504075

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Citation

Zhao, Y, Sun, R, You, L, Gao, C and Tian, Z (2003) Expression of leptin receptors and response to leptin stimulation of human natural killer cell lines. Biochem. Biophys. Res. Commun. 300:247-52

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.

Links

PubMed

Keywords

Cell Division/drug effects; Cell Line; Cytotoxicity, Immunologic; DNA-Binding Proteins/metabolism; Dose-Response Relationship, Drug; Gene Expression Regulation; Humans; Interleukin-2/biosynthesis; Interleukin-2/genetics; K562 Cells; Killer Cells, Natural/cytology; Killer Cells, Natural/drug effects; Killer Cells, Natural/immunology; Leptin/pharmacology; Membrane Glycoproteins/biosynthesis; Membrane Glycoproteins/genetics; Perforin; Pore Forming Cytotoxic Proteins; Receptors, Cell Surface/genetics; Receptors, Cell Surface/metabolism; Receptors, Leptin; STAT3 Transcription Factor; Trans-Activators/metabolism; Transcription, Genetic; Up-Regulation

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:LEP

involved_in

GO:0032814: regulation of natural killer cell activation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:LEP

involved_in

GO:0042269: regulation of natural killer cell mediated cytotoxicity

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:LEP

involved_in

GO:0032817: regulation of natural killer cell proliferation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

Notes

See also

References

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