TBTC induces adipocyte differentiation in human bone marrow long term culture

Organotins are widely used in agriculture and in 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 tributyltin (TBT) interacts with nuclear receptors PPAR¿ (peroxisome proliferator-activated receptor ¿) and RXR (retinoid x receptor) leading to adipocyte differentiation in the 3T3 cell line. Since adipocytes are known to influence hematopoiesis, for instance through the expression of cytokine 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 culture 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¿, but not RXR, mRNA was increased after 24h and 48h exposure. TBTC also induced a decrease in a number of chemokines, interleukins, and growth factors. Also the expression of leptin, a hormone involved in hematopoiesis, was decreased by TBTC treatment. So it appeared that TBTC induced adipocyte differentiation, while reducing a number of hematopoietic factors. This study indicates that TBTC may interfere in the hematopoietic process through an alteration of the stromal layer and cytokine homeostasis. Keywords: TBTC, adipocyte, bone marrow, leptin.

CARFI' Maria;  CROERA Cristina;  FERRARIO Daniele;  CAMPI Valentina;  BOWE Gerard;  PIETERS Raymond;  GRIBALDO Laura; 

2011-10-20

ELSEVIER IRELAND LTD

JRC43160

0300-483X,   

http://www.sciencedirect.com/science/article/pii/S0300483X08001613,    https://publications.jrc.ec.europa.eu/repository/handle/JRC43160,   

10.1016/j.tox.2008.03.025,