Cadmium ions promote monocytic differentiation of human leukemia HL-60 cells treated with 1α,25-dihydroxyvitamin D3.
Cadmium exposure has multiple effects on the immune system. These can be stimulating, leading to improved clearance of infections, or inhibiting, increasing susceptibility toward infectious agents. One in vivo observation in cadmium-exposed individuals is increased monocyte numbers. Therefore, the objective of this study is to investigate the impact of cadmium on monocyte differentiation in the HL-60 model cell line. Administered alone, cadmium had no effect. However, cadmium amplified the expression of monocyte surface markers CD11b and CD14 when differentiation was induced by 1α,25-dihydroxyvitamin D3 (VD3). Furthermore, differentiation with VD3 in the presence of cadmium augmented key monocyte functions: the capacities to perform phagocytosis and generate an oxidative burst. One important signaling pathway required for monocyte differentiation involves extracellular signal-regulated kinase (ERK)1/2. Notably, cadmium induced ERK1/2 phosphorylation in HL-60 cells. Furthermore, U0126, which inhibits ERK1/2 phosphorylation by upstream MAPK/ERK kinases (MEK)1/2, reduced VD3-mediated differentiation and abrogated the effects of cadmium. In conclusion, cadmium can augment monocytic differentiation by activating ERK1/2 signaling, leading to increased generation of functional monocytes. These increased monocyte numbers could contribute to the impact of cadmium on the immune system owing to their role in the production of pro-inflammatory cytokines and activation of T-cells by antigen presentation.
Ober-Blöbaum
Julia L
JL
Institute of Immunology, Medical Faculty, RWTH Aachen University, Pauwelsstrasse 30, Aachen, Germany.
Engelhardt
Gabriela
G
Hebel
Silke
S
Rink
Lothar
L
Haase
Hajo
H
D002104:Cadmium / Q000378:metabolism / Q000494:pharmacology; D002117:Calcitriol / Q000378:metabolism / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D002762:Cholecalciferol / Q000378:metabolism / Q000494:pharmacology; D018922:HL-60 Cells; D006801:Humans; D007477:Ions; D007938:Leukemia / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009000:Monocytes / Q000166:cytology / Q000378:metabolism; D010766:Phosphorylation; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000494:pharmacology
D007477:Ions; C118756:dihydroxy-vitamin D3; D002104:Cadmium; D014807:Vitamin D; D002762:Cholecalciferol; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D002117:Calcitriol