TBTC induces adipocyte differentiation in human bone marrow long term culture.
Organotins are widely used in agriculture and the chemical industry, causing persistent and widespread pollution. Organotins may affect the brain, liver and immune system and eventually human health. Recently, it has been shown that tri-butyltin (TBT) interacts with nuclear receptors PPAR gamma (peroxisome proliferator-activated receptor gamma) and RXR (retinoid x receptor) leading to adipocyte differentiation in the 3T3 cell line. Since adipocytes are known to influence haematopoiesis, for instance through the expression of cytokines and adhesion molecules, it was considered of interest to further study the adipocyte-stimulating effect of TBTC in human bone marrow cultures. Nile Red spectrofluorimetric analysis showed a significant increase of adipocytes in TBTC-treated cultures after 14 days of long term culture. Real-time PCR and Western blot analysis confirmed the high expression of the specific adipocyte differentiation marker aP2 (adipocyte-specific fatty acid binding protein). PPAR gamma, but not RXR, mRNA was increased after 24 h and 48 h exposure. TBTC also induced a decrease in a number of chemokines, interleukins, and growth factors. Also the expression of leptin, a hormone involved in haematopoiesis, was down regulated by TBTC treatment. It therefore appears that TBTC induced adipocyte differentiation, whilst reducing a number of haematopoietic factors. This study indicates that TBTC may interfere in the haematopoietic process through an alteration of the stromal layer and cytokine homeostasis.
Carfi'
M
M
ECVAM, IHCP, JRC, TP 580, via E. Fermi 2749, 21027 Ispra, Italy. maria.carfi@jrc.it <maria.carfi@jrc.it>
Croera
C
C
Ferrario
D
D
Campi
V
V
Bowe
G
G
Pieters
R
R
Gribaldo
L
L
D017667:Adipocytes / Q000166:cytology / Q000187:drug effects* / Q000473:pathology; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D015536:Down-Regulation; D004785:Environmental Pollutants / Q000633:toxicity*; D050556:Fatty Acid-Binding Proteins / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D006410:Hematopoiesis / Q000187:drug effects; D006801:Humans; D020738:Leptin / Q000235:genetics / Q000378:metabolism; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D047490:Retinoid X Receptor alpha / Q000235:genetics / Q000378:metabolism; D014220:Trialkyltin Compounds / Q000633:toxicity*
D016207:Cytokines; D004785:Environmental Pollutants; D050556:Fatty Acid-Binding Proteins; D020738:Leptin; D047495:PPAR gamma; D047490:Retinoid X Receptor alpha; D014220:Trialkyltin Compounds; C011559:tributyltin