The expression of adiponectin receptors and the effects of adiponectin and leptin on airway smooth muscle cells.
OBJECTIVE
Obesity is a major risk factor for asthma and it influences airway smooth muscle function and responsiveness. Adiponectin is inversely associated with obesity and its action is mediated through at least 2 cell membrane receptors (AdipoR1 and AdipoR2). Leptin is positively associated with obesity. We investigated whether human airway smooth muscle (ASM) cells express adiponectin receptors and whether adiponectin and leptin regulate human ASM cell proliferation and vascular endothelial growth factor (VEGF) release.


METHODS
Human ASM cells were growth- arrested in serum-deprived medium for 48 hours and then stimulated with PDGF, adiponectin and leptin. After 48 hours of stimulation, proliferation was determined using a cell proliferation ELISA kit. Human AdipoR1 and -R2 mRNA expressions were determined by RT-PCR using human- specific AdipoR1 and -R2 primers. Concentrations of VEGF, monocyte chemotactic protein (MCP)-1 and macrophage inflammatory protein (MIP)-1alpha in cell culture supernatant were determined by ELISA.


RESULTS
Both AdipoR1 and AdipoR2 mRNA were expressed in the cultured human ASM cells. However, adiponectin did not suppress PDGF-enhanced ASM cell proliferation, nor did leptin promote ASM cell proliferation. Leptin promoted VEGF release by human ASM cells, while adiponectin did not influence VEGF release. Neither leptin nor adiponectin influenced MCP-1 secretion from human ASM cells. Adiponectin and MIP-1alpha were not secreted by human ASM cells.


CONCLUSIONS
Human ASM cells expressed adiponectin receptors. However, adiponectin did not regulate human ASM cell proliferation or VEGF release, while leptin stimulated VEGF release by human ASM cells.
Shin
Joo Hwa
JH
Department of Pediatrics, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.
Kim
Jung Ho
JH
Lee
Won Young
WY
Shim
Jung Yeon
JY
D052242:Adiponectin / Q000378:metabolism / Q000494:pharmacology* / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism; D054405:Chemokine CCL3 / Q000378:metabolism; D006801:Humans; D020738:Leptin / Q000378:metabolism / Q000494:pharmacology* / Q000502:physiology; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D054419:Receptors, Adiponectin / Q000378:metabolism*; D012137:Respiratory System / Q000166:cytology / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
C475418:ADIPOR1 protein, human; C475420:ADIPOR2 protein, human; D052242:Adiponectin; D018932:Chemokine CCL2; D054405:Chemokine CCL3; D020738:Leptin; D010982:Platelet-Derived Growth Factor; D054419:Receptors, Adiponectin; D042461:Vascular Endothelial Growth Factor A