Regulation of dendritic cell function by insulin/IGF-1/PI3K/Akt signaling through klotho expression.
Insulin or insulin-like growth factor 1 (IGF-1) promotes the activation of phosphoinositide 3 kinase (PI3K)/Akt signaling in immune cells including dendritic cells (DCs), the most potent professional antigen-presenting cells for naive T cells. Klotho, an anti-aging protein, participates in the regulation of the PI3K/Akt signaling, thus the Ca2+-dependent migration is reduced in klotho-deficient DCs. The present study explored the effects of insulin/IGF-1 on DC function through klotho expression. To this end, the mouse bone marrow cells were isolated and cultured with GM-CSF to attain bone marrow-derived DCs (BMDCs). Cells were treated with insulin or IGF-1 and followed by stimulating with lipopolysaccharides (LPS). Tumor necrosis factor (TNF)-α formation was examined by enzyme-linked immunosorbent assay (ELISA). Phagocytosis was analyzed by FITC-dextran uptake assay. The expression of klotho was determined by quantitative PCR, immunoprecipitation and western blotting. As a result, treatment of the cells with insulin/IGF-1 resulted in reducing the klotho expression as well as LPS-stimulated TNF-α release and increasing the FITC-dextran uptake but unaltering reactive oxygen species (ROS) production in BMDCs. The effects were abolished by using pharmacological inhibition of PI3K/Akt with LY294002 and paralleled by transfecting DCs with klotho siRNA. In conclusion, the regulation of klotho sensitive DC function by IGF-1 or insulin is mediated through PI3K/Akt signaling pathway in BMDCs.
a Institute of Genome Research, Vietnam Academy of Science and Technology , Cau Giay , Ha Noi , Vietnam.
Nguyen Thi
NT
Xuan
a Institute of Genome Research, Vietnam Academy of Science and Technology , Cau Giay , Ha Noi , Vietnam.
Nguyen Huy
NH
Hoang
a Institute of Genome Research, Vietnam Academy of Science and Technology , Cau Giay , Ha Noi , Vietnam.
Vu Phuong
VP
Nhung
a Institute of Genome Research, Vietnam Academy of Science and Technology , Cau Giay , Ha Noi , Vietnam.
Nguyen Thuy
NT
Duong
a Institute of Genome Research, Vietnam Academy of Science and Technology , Cau Giay , Ha Noi , Vietnam.
Nguyen Hai
NH
Ha
a Institute of Genome Research, Vietnam Academy of Science and Technology , Cau Giay , Ha Noi , Vietnam.
Nong Van
NV
Hai
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects; D002867:Chromones / Q000008:administration & dosage; D003713:Dendritic Cells / Q000187:drug effects / Q000378:metabolism*; D003911:Dextrans / Q000008:administration & dosage; D016650:Fluorescein-5-isothiocyanate / Q000008:administration & dosage / Q000031:analogs & derivatives; D005786:Gene Expression Regulation / Q000187:drug effects; D005966:Glucuronidase / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D007328:Insulin / Q000235:genetics* / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000235:genetics* / Q000378:metabolism; D000090265:Klotho Proteins; D008070:Lipopolysaccharides / Q000008:administration & dosage; D051379:Mice; D009025:Morpholines / Q000008:administration & dosage; D051058:Oncogene Protein v-akt / Q000235:genetics* / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species; D015398:Signal Transduction / Q000187:drug effects
D002867:Chromones; D003911:Dextrans; D016650:Fluorescein-5-isothiocyanate; D005966:Glucuronidase; D007328:Insulin; D007334:Insulin-Like Growth Factor I; D000090265:Klotho Proteins; D008070:Lipopolysaccharides; D009025:Morpholines; D051058:Oncogene Protein v-akt; D019869:Phosphatidylinositol 3-Kinases; D017382:Reactive Oxygen Species; C015219:fluorescein isothiocyanate dextran; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
Dendritic cells; IGF-1; LPS; PI3K; insulin; klotho