Bisphenol A significantly enhances the neutrophilic differentiation of promyelocytic HL-60 cells.
Bisphenol A (BPA) is a well-known endocrine disruptor. However, little information is available on its immunological effects. To investigate the effect of BPA on leukocyte differentiation, we investigated its action on the neutrophilic differentiation of HL-60 cells induced by dimethylsulfoxide and granulocyte colony-stimulating factor (G-CSF) for 6 days. At low concentrations (10(-10)-10(-8) M), BPA significantly increased the superoxide production by differentiated HL-60 cells stimulated with opsonized zymosan (OZ) by about 20%, and expression of CD18, a component of the OZ-receptor, was increased to a similar extent by 10(-9) M BPA. To investigate the effect of BPA on the activity of PU.1, a transcription factor specific for granulocytic differentiation, we established a stable clone that expressed luciferase as a reporter of PU.1 activity. PU.1 activity increased during the neutrophilic differentiation of HL-60 cells, reaching a peak on day 3 and decreasing thereafter. Nanomolar BPA augmented the PU.1 activity on day 3 by about 60%. On the other hand, tamoxifen, a competitive inhibitor of estrogen receptors, did not suppress the effect of BPA on the differentiation of HL-60 cells. These results suggest that BPA exerts an enhancing effect on the neutrophilic maturation of leukocytes through an estrogen receptor-independent pathway. Long-term exposure to BPA might significantly affect the innate immunity of mammals, even at low doses.
Watanabe
Hidemi
H
National Institute of Health Sciences, 18-1 Kamiyoga 1-chome, Setagaya, Tokyo 158-8501, Japan. ksuzuki@nihs.go.jp
Adachi
Reiko
R
Kusui
Kaoru
K
Hirayama
Akiko
A
Kasahara
Tadashi
T
Suzuki
Kazuhiro
K
D001559:Benzhydryl Compounds; D018821:CD18 Antigens / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects* / Q000502:physiology; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D015870:Gene Expression / Q000187:drug effects; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D018922:HL-60 Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D009504:Neutrophils / Q000502:physiology*; D010636:Phenols / Q000494:pharmacology*; D010750:Phosphoproteins / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism; D013629:Tamoxifen / Q000494:pharmacology; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D015054:Zymosan / Q000494:pharmacology; D000099232:Proto-Oncogene Protein Spi-1; D000098826:Bisphenol A Compounds
D001559:Benzhydryl Compounds; D018821:CD18 Antigens; D004121:Dimethyl Sulfoxide; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D010636:Phenols; D010750:Phosphoproteins; D011518:Proto-Oncogene Proteins; D013481:Superoxides; D013629:Tamoxifen; D015534:Trans-Activators; D015054:Zymosan; D000099232:Proto-Oncogene Protein Spi-1; C079789:neutrophil cytosol factor 67K; C006780:bisphenol A; D000098826:Bisphenol A Compounds